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PubMed1999

The immune system in the elderly: I. Specific humoral immunity.

Profound and complex changes in the immune response occur during the aging process. Immunosenescence is reflected by a sum of disregulations of the immune system and its interaction with other systems. Many of the changes would appear to implicate age-related deficiencies of the immune responses. The term immunosenescence designates therefore a sort of deterioration of the immune function which is believed to manifest itself in the increased susceptibility to cancer, autoimmune disease, and infectious disease. Evidence has been accumulating from several studies which suggest an association between immune function and individual longevity. However, there are observations, especially in very old healthy people, that several immune functions are unexpectedly well preserved and substantially comparable to those observed in young subjects. These findings raise the question of whether the alterations that can be observed in the immune parameters of the elderly are a cause or a result of underlying disease processes. Moreover, studies on centenarians revealed a remodeling of the immune system rather than a deterioration, suggesting that the changes observed during immunosenescence do not correspond to immunodeficiency. The underlying mechanisms of these events are however still unclear. The purpose of the present review is to assess the status of research on the immunobiology of aging. In this first section, we focus attention on the B cell biology of aging. In clinical practice, the changes in humoral immune responsiveness and antibody-mediated defense mechanisms could greatly influence the incidence and outcome of bacterial infections and autoimmune diseases as well as the response to vaccines.

Aged↗

PubMed2000

MUC1-specific immune responses in human MUC1 transgenic mice immunized with various human MUC1 vaccines.

Analyses of MUC1-specific cytotoxic T cell precursor (CTLp) frequencies were performed in mice immunized with three different MUC1 vaccine immunotherapeutic agents. Mice were immunized with either a fusion protein comprising MUC1 and glutathione S-transferase (MUC1-GST), MUC1-GST fusion protein coupled to mannan (MFP) or with a recombinant vaccinia virus expressing both MUC1 and interleukin-2. Mouse strain variations in immune responsiveness have been observed with these vaccines. We have constructed mice transgenic for the human MUC1 gene to study MUC1-specific immune responses and the risk of auto-immunity following MUC1 immunization. Transgenic mice immunized with MUC1 were observed to be partially tolerant in that the MUC1-specific antibody response is lower than that observed in syngeneic but non-transgenic mice. However, a significant MUC1-specific CTLp response to all three vaccines was observed, indicating the ability to overcome T cell, but to a lesser extent B cell, tolerance to MUC1 in these mice. Histological analysis indicates no evidence of auto-immunity to the cells expressing the human MUC1 molecule. These results suggest that it is possible to generate an immune response to a cancer-related antigen without damage to normal tissues expressing the antigen.

Animals↗

PubMedDate not supplied

Immunization of baboons with attenuated schistosomula of Schistosoma haematobium: levels of protection induced by immunization with larvae irradiated with 20 and 60 krad.

We have shown previously that baboons (Papio anubis) develop high levels (greater than 80%) of protection against challenge infection following immunization with Schistosoma haematobium cercariae irradiated with 20 krad. In the present study baboons were immunized with schistosomula irradiated with either 20 krad or 60 krad, with variations in the timing and number of larvae comprising each vaccination. Baboons immunized 2 or 3 times with schistosomula irradiated with 20 krad were significantly more protected (85-90%) against challenge infection than baboons similarly immunized with larvae receiving 60 krad (56-50% protection). Baboons immunized with schistosomula irradiated with 20 krad were better protected against challenge infection at 8 weeks after immunization than at 28 weeks after immunization. Protection was manifest by a reduction in worm numbers, tissue and excreta egg counts, gross pathology and, to a lesser extent, by stability of body weight and haematological indices following challenge. Enzyme-linked immunosorbent assay (ELISA) results of selected baboon sera showed few differences related to irradiation dose alone, but titres were higher in baboons receiving booster immunizations, and there was a significant correlation between titres immediately preceding challenge and the degree of resistance. Examination of responses to individual schistosomular surface antigens by immunoprecipitation and sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed no correlation between the pattern of antigens recognized and resistance status. As with the ELISA assay, an anamnestic response was detected after vaccination, while the amount of antibody present declined markedly with increasing time after individual immunizations.

Animals↗

PubMed1988

Cells involved in the immune response. XXXV. The antigen-specific antibody response in the rabbit is suppressed by thymocytes of allogeneic immunized rabbits (ITSC) and by the non-toxic suppressor factor (ITSF) secreted by these thymocytes.

The antigen-specific suppressor cells (ITSC) detected in the thymus of the rabbit 7 days post-iv immunization with sheep or horse erythrocytes (SRBC and HRBC, respectively), and the antigen-specific suppressor factor (ITSF) which the ITSC secrete in culture, inhibit the antigen-specific primary immune response in vivo when injected iv into SRBC and/or HRBC immunized rabbits on Days 0, 3, and 5 (ITSC) or daily on Days 0 to 5 (ITSF) post-primary immunization. The rabbits recover the ability to synthesize the specific antibodies following reimmunization by day 80 post-primary immunization. The primary immune response toward a non-cross-reacting antigen is not inhibited by the antigen-specific ITSC or ITSF. Neither the thymocytes of unimmunized rabbits nor the secretions of these cells in culture can suppress the primary immune response in vivo to either SRBC or HRBC. It must be emphasized that the suppression of the immune response by ITSC and ITSF in the rabbit is antigen-specific. ITSC and ITSF are not cytotoxic to rabbit lymphocytes in vitro. No gross or microscopic changes were detected in any of the lymphoid and nonlymphoid organs of rabbits sacrificed 2 days following 5 daily iv injections of large doses (10 ml) of ITSF. ITSF causes no adverse reaction in vivo since it did not induce morbidity in the rabbits during the 80 days observation period following its injection iv daily for 5 days commencing with the primary immunization.

Animals↗

PubMed1987

Immunization against East Coast fever: the use of selected stocks of Theileria parva for immunization of cattle exposed to field challenge.

Two antigenically different stocks of Theileria parva parva (Kilifi and Marikebuni), previously characterized as belonging to groups A and C respectively on monoclonal antibody (MAb) profiles, were selected for immunization of different breeds of cattle against East Coast fever (ECF) by the infection and treatment method. A total of 52 immunized cattle and 33 susceptible controls of different group sizes were exposed to field challenge by ticks for periods of 42-90 days at three field sites where ECF is endemic on the Kenyan coast. All immunized cattle survived ECF challenge, but 87% of the controls died of the disease. The cattle exposed at one site had been immunized 1 year earlier and maintained tick-free in the intervening period. The level of immunity in these cattle was similar to that of cattle which had been immunized 1 or 2 months prior to exposure. Thus, immunity had not waned over the 1-year period. A study at another site showed that acaricidal treatment of immunized cattle could be safely extended from twice a week to once every three weeks, whereas in susceptible cattle even twice weekly spraying did not control ECF. The isolates made from infected controls during the trials indicated the presence of three T. p. parva stocks as defined by MAb profiles. Of the two stocks used for immunization, T. p. parva Marikebuni induced broader protection. In view of the apparent limited antigenic diversity of T. p. parva strains within the Coast Province it is suggested that the Marikebuni stock might represent a key stock for vaccination in this area.

Animals↗

PubMed2006

Prime-boost immunization with DNA followed by a recombinant vaccinia virus expressing P50 induced protective immunity against Babesia gibsoni infection in dogs.

A heterologous prime-boost immunization regime with priming DNA followed by recombinant vaccinia virus expressing relevant antigens has been shown to induce effective immune responses against several infectious pathogens. In this study, we constructed a recombinant plasmid and vaccinia virus, both of which expressed P50 of Babesia gibsoni, to investigate the immunogenicity and protective efficacy of a heterologous prime-boost immunization against canine babesiosis. The dogs immunized with the prime-boost regime developed a significantly high level of specific antibody against P50 when compared with the control groups, and the antibody level was strongly increased after a booster immunization with a recombinant vaccinia virus. The prime-boost immunization regime induced a specific IgG2 antibody response and IFN-gamma production in dogs. Two weeks after the booster immunization with a recombinant vaccinia virus expressing P50, the dogs were challenged with B. gibsoni patasites. The dogs immunized with the prime-boost regime showed partial protection, manifested as a significantly low level of parasitemia and a 2-day delay of the peak parasitemia. These results indicated that such a heterologous prime-boost immunization approach might be useful against B. gibsoni infection in dogs.

Animals↗

PubMed1985

Cluster formation in a symmetrical network: a dynamical system for the description of the suppression among non-immune T lymphocytes and its application to the effects of immunization.

A mathematical model has been developed for the description of the suppressive regulation between polyclonally activated normal and immune T cells. The model assumes reversible cell-cell interactions to interpret results from limiting dilution experiments performed to determine the frequencies of precursor cells for antigen-specific T effector lymphocytes and to analyse mechanisms regulating the maturation of precursor into effector T cells. In particular, the model deals with the changes induced in the T lymphocytes population following immunization with antigens. In these limiting dilution experiments, T cells are placed in cultures at varying cell numbers with all other essential culture constituents kept in excess. After polyclonal activation of the T cells in culture they are supplied with growth and maturation factors so that they form daughter clones of functionally active T effector cells. The typical result observed was that effector T cells develop in cultures at low cell input but that this development is totally suppressed at high cell numbers. This result suggested that, at high cell numbers, the effector T cells are exposed to a sufficient number of other T cells of appropriate specificity to permit suppressive interactions. Whereas this is the case for non-immune T cells, T cells after immunization develop into effector cells both at high as well as at low cell concentrations, though with efficiencies less than proportional to their number of precursors. Our mathematical model is made up of a set of first order autonomous ordinary differential equations in many variables permitting the calculations of numbers of free cells and of cells engaged in cellular clusters of varying sizes. Free cells can develop into effector cells whereas cells engaged in clusters cannot. We calculate the consequences of several reasonable hypotheses concerning the effects of immunization. We consider the possibility that immunization modifies the growth behavior of the antigen-specific cells to permit an increased or accelerated clonal expansion in culture. Alternatively, we consider the possibility that immunization changes the interaction strength between cells specific for the immunizing antigen and other cells. Thirdly, we have connected both behaviors by calculating the case of an inverse relationship between growth rates and intensities of interaction between cells. Our model has been inspired by the symmetrical network model and can be interpreted in this framework. It proposes that immune regulation is a consequence of idiotype-anti-idiotype interactions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2002

Characterization of humoral and cellular immune responses in mice induced by immunization with HIV-1 Nef regulatory protein encapsulated in poly(DL-lactide-co-glycolide) microparticles.

We have characterized the humoral and cellular immune responses of BALB/c mice immunized with HIV-1 Nef regulatory protein encapsulated in poly(DL-lactide-co-glycolide) PLG particles. Three groups of mice were immunized with Nef PLG, Nef in the presence of complete Freund's adjuvant (CFA) or Nef alone in PBS. When titers were compared 7 months after the last injection, anti-Nef titers in mice immunized with Nef PLG were still close to the maximum, whereas a significant decrease was observed in mice immunized with Nef alone (five times lower) or with Nef in CFA (three times lower). These results indicate that Nef PLG is at least a similar or better vector/adjuvant than Nef in CFA concerning the duration of the humoral immune response. The analysis of cytokine profiles (IL-5 and IL-10) and the isotypic patterns of anti-Nef antibodies (predominantly IgG1), in the three groups of mice, indicated a predominant Th2 immune response. Using synthetic peptides covering the entire sequence of Nef, we identified at least three linear epitopes within sequences 32-64, 118-167 and 185-205 in the sera of mice immunized with Nef PLG or Nef CFA. In contrast, anti-Nef antibodies against Nef alone failed to recognize synthetic peptides, indicating that the majority of anti-Nef antibodies were primarily directed against conformational epitopes. We then examined the ability of Nef PLG to prime for the antigen-specific proliferative responses in vitro. The data obtained indicate the presence of both B-cell and T-cell epitopes in the C-terminal fragment of the protein after immunization of mice with Nef encapsulated in PLG particles.

Animals↗

PubMed2002

Intranasal immunization with recombinant outer membrane protein P6 induces specific immune responses against nontypeable Haemophilus influenzae.

OBJECTIVE: Nontypeable Haemophilus influenzae (NTHi) is one of the leading causative pathogens for otitis media. The outer membrane protein P6 of NTHi is highly conserved among the strains and is an attractive candidate for a preventive vaccine. However, for the production of a relatively small amount P6 containing lipopolysaccharides, the development of a recombinant version of this protein is required. This study was designed to investigate the specific mucosal immunity induced by intranasal immunization of recombinant P6 (rP6) with cholera toxin (CT). METHODS: BALB/c mice were immunized with of rP6 (30 microg) and CT (2 microg) intranasally every 2 days for 2 weeks. Anti-rP6 specific IgG, IgA and IgM antibodies and the subclass of anti-rP6 specific IgG antibody were determined by enzyme linked immunosorbent assay (ELISA). Anti-rP6 specific IgA in nasopharyngeal washings were also determined by ELISA. Nasopharyngeal clearance of inoculated NTHi after the intranasal immunization were assessed. All statistical differences between the two groups were assessed by ANOVA parametric test. RESULTS: Intranasal immunization with rP6 and CT evoked rP6-specific mucosal IgA immune response as well as the systemic IgG immune response against rP6 and enhanced nasopharyngeal clearance of inoculated live NTHi. CONCLUSION: These results indicate the good immunogenicities of rP6 to induce specific immune responses against NTHi. Intranasal immunization with rP6 will be an effective approach to protect infections of NTHi.

Analysis of Variance↗

PubMed2001

Immune responses and protection in different strains of aged mice immunized intranasally with an adjuvant-combined influenza vaccine.

Immune responses and protection against influenza virus infection were compared between young (2 months) and aged (18 months) BALB/c, C3H and C57BL/6 (B6) mice after intranasal vaccination. The mice were immunized with 2.5 microg protein of A/PR/8/34 (PR8) (H1N1) virus vaccine containing a cholera toxin adjuvant. In both the young and aged BALB/c mice, high levels of PR8-specific antibody-forming cell (AFC) responses were induced in the nasal-associated lymphoid tissue (NALT) 7 days after immunization. Nasal wash IgA and serum IgG antibody (Ab) responses to the PR8 haemagglutinin (HA) 4 weeks after immunization were slightly higher in the young mice than in the aged mice. The young mice showed complete protection against challenge infection, while the aged mice showed only a partial protection. In the C3H mice, NALT-AFC, and IgA and IgG Ab responses were higher in the young mice than those in the aged mice in parallel with the more efficient protection in the young mice than in the aged mice. Both the young and aged B6 mice showed no NALT-AFC responses, scarce IgA and IgG Ab responses and no protection. In the BALB/c mice, IgG1 and IgG2a levels were significantly lower in the aged mice. On the other hand, in the C3H mice, only IgG2a level was significantly lower in the aged mice. Similar results were obtained in terms of immune responses and protection between the young and aged mice of three different strains of mice after intra-nasal immunization with 0.1 microg of PR8 vaccine containing the adjuvant, two-times at 4-week intervals. In the B6 mice, the immune response was improved by immunization with a higher dose of the adjuvant-combined vaccine. These results suggest that local Ab responses, as well as systemic Ab responses, are downregulated in aged mice, although the degree of the downregulation of immune responses differs from strain to strain.

Adjuvants, Immunologic↗

PubMed2001

Immune dysfunction and immune restoration disease in HIV patients given highly active antiretroviral therapy.

BACKGROUND: Some immune defects caused by HIV infection resolve following treatment with highly active antiretroviral therapy (HAART), but residual immune dysfunction may cause disease. Problems with the regulation of the restored immune system in the first six months of treatment can lead to atypical presentations of mycobacterial, cytomegalovirus (CMV), hepatitis B virus or hepatitis C virus (HCV) disease. We defined these conditions as immune restoration diseases (IRD) and showed that they occur in 30-40% of individuals who begin HAART from low CD4 T cell counts. OBJECTIVES: Analysis of immune dysregulation in patients who have responded to HAART. STUDY DESIGN: Patients with successful immune reconstitution following HAART were selected from a database containing details of all patients managed at Royal Perth Hospital (Western Australia) on the basis a CD4 T cell count <100/microl before HAART and an increase of >4-fold or to >200 CD4 T cells/microl. RESULTS: Patients who had experienced an IRD demonstrated increased levels of bioavailable IL-6 and increased expression of CCR5 and CCR3 on monocytes and granulocytes, but numbers of gammadeltaT-cells were similar to patients with similar CD4 T cell counts without an IRD. Carriage of HLA-A2, -B44 was associated with a history of CMV retinitis and/or encephalomyelitis as an IRD, but not with IRD initiated by Mycobacterium sp., cutaneous varicella zoster or herpes simplex infections or HCV. We also identified a patient with Graves' thyrotoxicosis and pronounced lymphadenopathy after HAART, and demonstrated that thyroid stimulating hormone receptor antibody production was associated with an increase in serum soluble CD30, suggesting acquired immune dysregulation. CONCLUSIONS: IRD are associated with persistent immune activation, where differences in genetic profiles suggest that distinct pathological mechanisms are responsible for retinitis/encephalomyelitis IRD. Further studies are important as dysregulated T-cell responses may cause disease later in the course of immune reconstitution.

AIDS-Related Opportunistic Infections↗

PubMed2006

Analysis of humoral immunity of hepatitis D virus DNA vaccine generated in mice by using different dosage, gene gun immunization, and in vivo electroporation.

BACKGROUND: Hepatitis D virus (HDV) DNA vaccine can produce Th1 and cytotoxic T-cell immune responses but only a low anti-HDV antibody titer is generated with a large hepatitis D antigen (L-HDAg) construct. In contrast, DNA vaccine expressing small hepatitis D antigen (S-HDAg) can generate a high titer of anti-HDV antibodies. Whether the low humoral immunity of L-HDAg DNA vaccine is due to inadequate dosage or can be ameliorated by other modes of immunization needs further evaluation. METHODS: Plasmid (p25L) encoding L-HDAg and plasmid (pS/p25L) coexpressing hepatitis B surface antigen (HBsAg) and L-HDAg were used in this study. We compared the humoral response generated in mice using different plasmid DNA dosages and modes of immunization, including gene gun and in vivo electroporation (EP). RESULTS: Intramuscular injection with a high dose of plasmid DNA (10 mg/kg) produced strong antibodies to HBsAg earlier than the usual dose did, but did not augment the anti-HDV response. Gene gun DNA immunization could not provide a better humoral immune response to HDV. EP DNA immunization had a higher anti-HDV seroconversion rate of 80%, but the anti-HDV antibody responses were generally weak (titer < or = 400:1). CONCLUSION: The low humoral immunogenicity of DNA vaccine with L-HDAg cannot be ameliorated by different dosage, gene gun immunization, or in vivo EP intramuscular injection. DNA vaccine with a L-HDAg construct may not be a candidate HDV vaccine to generate anti-HDV humoral immunity.

Animals↗

PubMed1985

Studies on the abomasal pathology of immunized and non-immunized sheep infected with Haemonchus contortus.

Five adult ewes and five lambs were repeatedly immunized with weekly doses of 10,000 irradiated Haemonchus contortus L3 before challenge with 100,000 and 10,000 normal larvae respectively. Two groups of non-immunized ewes and lambs were similarly challenged and one animal from each of the four groups killed on days 3, 5, 7, 10 and 24 post-challenge. The cellular changes in the abomasal mucosa were less marked in the non-immunized groups than in the immunized animals and appeared later in the lambs than in the ewes. Thus, in the immunized ewes increases in the numbers of mast cells and eosinophils were evident within five days of challenge whereas similar changes appeared later in the immunized lambs. Also marked lymphoid aggregates at the base of the mucosa and in the submucosa were detected only in the immunized ewes. However, both immunized and non-immunized ewes showed rises in the numbers of IgA plasma cells after challenge which were not evident in either group of lambs.

Abomasum↗

PubMed1999

A preschool immunization project to enhance immunization levels, the public-private relationship, and continuity of care.

This study was conducted to determine whether implementing a program aimed at providing a variety of incentives to physicians who provide immunizations to preschool-aged children would help to improve immunization rates and reduce fragmented care for patients. Twenty physicians from 14 private practices that provide care to preschool-aged children from low income families in suburban Cook County, Illinois participated in the project. A randomly selected subset of patient case records from the physicians' offices were audited after the implementation of the project to determine the immunization status of children in the practices and the nature of services provided. These 310 records of children under three years of age who were treated between 1991-1994 (the intervention sample) were compared to 310 charts from a 1988-1990 cohort of records (baseline sample). The groups did not differ on race or gender; however, significantly more families in the 1988 through 1990 cohort of children under 3 years of age were insured privately when compared to the 1991 through 1994 cohort. Seventy percent (218) of the records in the intervention sample were up to date for age on immunizations compared to 45% (141) of the baseline records, reflecting a statistically significant difference (p < .00001). The intervention sample showed significantly more well child visits where immunizations were given and follow up visits where immunizations were given when compared to the baseline sample. Physicians completed surveys before and after implementation of the project. They were questioned about their knowledge and practices regarding immunizations as well as their opinion of specific project components. All of the physicians viewed the project as an effective means to improve immunization services to low income children. The project demonstrates a potential means of enhancing immunization levels and continuity of care among preschool-aged children. It also highlights the workable nature of the partnership between public and private sectors.

Child Health Services↗

PubMed2003

Modulation of cellular immune response against hepatitis C virus nonstructural protein 3 by cationic liposome encapsulated DNA immunization.

A vaccine strategy directed to increase Th1 cellular immune responses, particularly to hepatitis C virus (HCV) nonstructural protein 3 (NS3), has considerable potential to overcome the infection with HCV. DNA vaccination can induce both humoral and cellular immune responses, but it became apparent that the cellular uptake of naked DNA injected into muscle was not very efficient, as much of the DNA is degraded by interstitial nucleases before it reaches the nucleus for transcription. In this paper, cationic liposomes composed of different cationic lipids, such as dimethyl-dioctadecylammonium bromide (DDAB), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), or 1,2-dioleoyl-sn-glycerol-3-ethylphosphocholine (DOEPC), were used to improve DNA immunization in mice, and their efficiencies were compared. It was found that cationic liposome-mediated DNA immunization induced stronger HCV NS3-specific immune responses than immunization with naked DNA alone. Cationic liposomes composed of DDAB and equimolar of a neutral lipid, egg yolk phosphatidylcholine (EPC), induced the strongest antigen-specific Th1 type immune responses among the cationic liposome investigated, whereas the liposomes composed of 2 cationic lipids, DDAB and DOEPC, induced an antigen-specific Th2 type immune response. All cationic liposomes used in this study triggered high-level, nonspecific IL-12 production in mice, a feature important for the development of maximum Th1 immune responses. In conclusion, the cationic liposome-mediated gene delivery is a viable HCV vaccine strategy that should be further tested in the chimpanzee model.

Animals↗

PubMed1984

Antimalarial immunity in Saimiri monkeys. Immunization with surface components of asexual blood stages.

Plasmodium falciparum polypeptides of 200 and 140 K mol wt exposed at the surface of merozoites and/or schizonts were purified by affinity chromatography and by electroelution from sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Monkeys were separated into three groups of four and immunized either with one of the two polypeptides or with saline (control). After intravenous challenge with 2.5 X 10(7) P. falciparum asexual blood stages, two monkeys of the control group had to be treated and two recovered spontaneously after peak parasitemia of 9 and 11%. The four monkeys immunized with the 140 K polypeptide recovered without treatment after peak parasitemia between 1.5 and 4.5%. Monkeys immunized with the 200 K polypeptide had similar peak parasitemia except one monkey who suffered from a large skin excoriation and who recovered spontaneously after a peak parasitemia of 11%. Prechallenge sera of the immunized monkeys reacted only with the polypeptide used for immunization except for one serum of the 140 K group, which precipitated an additional polypeptide of 39 K, and a polypeptide of 31 K weakly precipitated by the four sera of monkeys immunized with the 200 K polypeptide. The relatedness between the 200 and 140 K polypeptides was investigated using tryptic digestion and reverse phase chromatography. No clear analogy was found between the two polypeptides, which suggests that immunization with either of two independent surface components of P. falciparum asexual blood stages is able to induce at least a partial protective immunity in immunized hosts.

Animals↗

PubMed1998

Genetic immunization with glycoprotein 63 cDNA results in a helper T cell type 1 immune response and protection in a murine model of leishmaniasis.

Genetic immunization is a promising gene therapy approach for the prevention and treatment of infectious disease. Plasmid DNA expressing genes of pathogens is directly introduced into host cells and specific cell-mediated and/or humoral immune responses are elicited against the encoded protein. Leishmaniasis is a significant world-wide health problem for which no vaccine exists. In susceptible animals, such as BALB/c mice, protection from leishmaniasis requires induction of a Thl immune response. In this study, cell-mediated immunity to Leishmania major (L. major) was induced by injecting BALB/c mice intradermally with plasmid DNA expressing the conserved L. major cell surface glycoprotein gp63 (gp63-pcDNA-3). CD4 T lymphocytes from gp63-pcDNA-3-immunized mice proliferated and produced IFN-gamma (but not IL-4) when stimulated in vitro with freeze-thawed parasites, consistent with a Th1 immune response. In contrast, lymphocyte proliferation in animals immunized with freeze-thawed parasites was associated with IL-4 (but not IFN-gamma) production, suggesting a nonprotective Th2 response. Challenge studies revealed that gp63-pcDNA-3 vaccination protected 30% of susceptible mice (21 of 70) from Leishmania infection while neither gp63 protein (0 of 20) nor freeze-thawed parasite vaccines (0 of 50) were efficacious. Dendritic cells derived from skin of gp63-pcDNA-3-injected mice also immunized naive recipients and protected them from leishmaniasis. We conclude that gp63-pcDNA-3 genetic vaccination results in a CD4-dependent Th1 immune response that correlates with protection from disease, and suggest that skin-derived dendritic cells are involved in priming this response.

Adoptive Transfer↗

PubMed1977

Specificity of antitumor immune reactions mediated by xenogeneic immune RNA.

Evidence that xenogeneic immune RNA (I-RNA) mediated specific cytotoxic immune responses against human tumor-associated antigens was obtained from in vitro studies in two autologous melanoma systems. In these systems, malignant melanoma target cells, matching normal fibroblast target cells, lymphocyte effector cells, and melanoma and normal skin tissue used to immunize RNA donor animals were derived from the same autochthonous hosts. When incubated with autologous lymphocytes, I-RNA extracted from the lymphoid organs of donor animals immunized with melanoma tissue mediated immune reactions against autologous melanoma target cells in vitro. I-RNA from animals immunized with normal skin tissue from autochthonous hosts did not increase the cytotoxicity of autologous lymphocytes for autologous melanoma cells. Using autologous fibroblasts as target cells, we detected no increase in cytotoxicity when autologous lymphocytes were incubated with RNA from animals immunized either with melanoma tissue or normal skin tissue from the autochthonous host. By contrast, when allogeneic lymphocytes were used as effector cells, RNA extracted from animals immunized either with melanoma tissue or normal skin mediated cytotoxic immune reactions against melanoma target cells and normal fibroblast target cells derived from the same patient.

Antigens, Neoplasm↗