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Characterization of the cellular immune response in American cutaneous leishmaniasis.

The in vitro and in vivo cellular immune reactivity of 49 patients with American cutaneous leishmaniasis (ACL) was evaluated using mitogens and parasite antigens. Patients were examined before treatment and were classified on the basis of clinical and histopathological criteria as suffering localized cutaneous leishmaniasis (LCL, 32 patients) or mucocutaneous leishmaniasis (MCL, 11 patients). A small group (6 patients) of treated diffuse cutaneous leishmaniasis (DCL) patients was also examined. The lymphocyte proliferative responses to PHA were significantly lower than those of controls (87 individuals, from either endemic or nonendemic zones) in LCL, and particularly MCL. Con A responses were, however, effectively normal in these patients. Both in vivo and in vitro cellular immune responses to leishmanial antigens were significantly greater in MCL and LCL patients than in the controls, the intensity of the reactions being by far the greatest in MCL. DCL patients demonstrated a complete absence of specific immune responsiveness both in vivo and in vitro. The significance of these results in the mechanisms leading to the resolution of the infection or production of pathologic lesions is discussed.

Adolescent↗

Essential edema-proteinuria-hypertension (EPH) gestosis and gestosis superimposing pre-existing renal disease: comparison of cellular immunity parameters.

The paper is aimed at evaluation of certain indices of cellular immunity in pregnant women with gestosis superimposing pre-existing renal diseases and comparing them with the immunological condition of women with essential gestosis. T lymphocyte subpopulations and lymphocyte proliferative responses to mitogens (phytohemagglutinin--PHA, concanavalin A--Con A and pokeweed mitogen--PWM) in the fetal calf serum and autological sera were studied. The groups of examined pregnant women in the 3rd trimester did not vary with regard to gestation age, calendar age and to the severity of edema (E), proteinuria (P) and hypertension (H) gestosis symptoms. It has been found that equal changes occur in both groups of women, regarding the examined indices of cellular immunity, when referred to normal pregnant women. In the gestotic women a decreased absolute and percentage content of CD8+ T cells and increased percentage of CD3+ and CD4+ lymphocytes were found in comparison with the normal pregnant women, which led to an almost 2.5-fold increase of CD4+/CD8+ ratio. The sera of gestotic women, in comparison with the healthy pregnant group, strongly increased the proliferation of Con A and PWM-induced lymphocytes. It may then be assumed that the observed immunological changes do not coincide with the primary causes of gestosis. We suggest that immunological factors largely contribute to the development of essential gestosis and gestosis superimposing pre-existing renal disease.

Adult↗

Effect of influenza A virus infection on natural and adaptive cellular immunity.

Influenza A virus (FLU) is an important pathogen in humans. Although many features of the antiviral immune response have been elucidated in murine and human models of disease, little is known about the role of NK cells, which provide natural, innate immunity. The effects of experimental intranasal FLU (H1N1) inoculation on NK cells and other immune parameters were studied in 18 healthy, adult volunteers during the acute and convalescent phases of infection. Peripheral blood mononuclear cells (PBMNC) were assayed at baseline and on Postinoculation Days 1, 3, 4, 6, 7, 23, and 44. FLU infection and pathophysiologic upper airway responses were documented in all subjects, and there was no mortality. During both the acute (Days 1-3) and the convalescent (Days 23 and 44) stages of the FLU infection, significant increases in NK activity and decreases in the number of activated NK cells were observed. Reductions in the absolute number of T lymphocytes and in PBMNC proliferation to FLU virus antigen and mitogen were also observed. The current investigation extended those findings to include reductions in the number of CD4+ and CD8+ T lymphocytes and increases in the number of activated T lymphocytes. These results document that FLU infection was accompanied by enhancement of natural immunity and, as expected, suppression of most of the other measured parameters of cellular immunity. The normal response to FLU infection in humans may involve sequential modulation of the different components of the cellular immune system.

Adult↗

Achievement of cellular immunity and discordant xenogeneic tolerance in mice by porcine thymus grafts.

Specific cellular immune tolerance may be essential for successful xenotransplantation in humans. Thymectomized (ATX), T and NK cell-depleted immunocompetent mice grafted with xenogeneic fetal pig thymic and liver tissue (FP THY/LIV) result in efficient mouse thymopoiesis and peripheral repopulation of functional mouse CD4(+) T cell. Very importantly, the reconstituted mouse T cells are specifically tolerant to pig donor antigens. Studies demonstrated that porcine MHCs mediated positive and negative selection of mouse thymocytes in FP THY grafts, whereas mouse MHCs were involved in negative selection in grafts. Therefore, T cell tolerance to xenogeneic donor antigens could be induced by grafting donor thymus tissue. Xenogeneic thymic replacement might have a potential role in the reconstitution of cellular immunity in patients with AIDS or other immunodeficiencies caused by thymus dysfunction.

Acquired Immunodeficiency Syndrome↗

Evidence for the involvement of corticosterone in the ontogeny of the cellular immune apparatus of the mouse.

The effects of corticosterone deprivation in the cellular immune system of the mouse have been studied. Adrenalectomy was performed from three weeks after birth; at an earlier age oral administration of aminoglutethimide phosphate (AGP) had to be used. Three effects could be recognized: (1) Adrenalectomy or AGP treatment, at any age studied, resulted in an enhanced delayed hypersensitivity (DH) to sheep red blood cells (SRBC). This effect has previously been ascribed to monocytes. (2) An altered T lymphocyte distribution was observed as consequence of early adrenalectomy or continuous AGP administration. The lymph nodes were depleted whereas the thymus was increased in size and blood-leucocytes increased in number. This effect appeared reversible on restoration of adrenal function. (3) Irreversible damage to the cellular immune system following early AGP intake was observed in DH after recovery of the adrenal function. As corticosterone is the principal glucocorticoid produced by mice the effects described under (2) and (3) may be ascribed to this hormone. Our results suggest that thymic involution during life, is at least partially, under adrenal control.

Adrenal Glands↗

Humoral and cellular immunity in patients with hepatic alveolar echinococcosis. A 2 year follow-up with and without flubendazole treatment.

Parameters of humoral and cellular immunity were assessed in 12 patients with alveolar echinococcosis (AE) of the liver before, during and after discontinuation of treatment with flubendazole (FZ). In infected patients, before any medical treatment values of serum IgG, IgA, total haemolytic complement and C4 were significantly higher than those observed in control subjects; IgA levels were higher in jaundiced patients. Specific antibodies assayed by indirect haemagglutination and immunoelectrophoresis were present only in infected patients and were shown to decrease by the sixth month of treatment; however, similar fluctuations were observed without treatment. The percentage and absolute number of B lymphocytes, and total circulating lymphocytes, were significantly lower in patients with AE. An impairment of functional activity of T cells assayed by the leucocyte migration test, with PPD and Candidin as antigens, was demonstrated despite a normal percentage of SRBC rosettes. The 'score' of migration index still decreased during FZ treatment and returned to initial values after the year of follow-up without treatment. These results suggest that human AE is associated with important immunological disturbances. Changes in humoral immunity can be unequivocally considered to be a consequence of the parasite infection. The primary or secondary nature of the impairment of cellular immune responses and its mechanisms remain to be elucidated. Flubendazole could be responsible for an increase of cellular immune alterations in these patients.

Adult↗

Correlation between in vivo humoral and in vitro cellular immune responses following immunization with hepatitis B surface antigen (HBsAg) vaccines.

To study the regulation of the human immune response to hepatitis B surface antigen (HBsAg) we have carefully monitored the in vivo humoral and in vitro cellular immune responses to HBsAg in 50 subjects receiving four doses of hepatitis B vaccine according to a 0, 1, 2, 12 month vaccination scheme. Twenty-three subjects were given a plasma-derived vaccine (Hevac B) and 27 received a recombinant HBsAg vaccine (yeast-derived; Engerix-B). The humoral and cellular immune responses were measured before vaccination (day 0); 6 days after the second dose (day 36); 6 days (day 66), 2 months (day 120) and 10 months (day 365) after the third dose and 1 month after the fourth dose (day 395). Based on the kinetics of the humoral immune responses, the vaccinees could be classified into fast, intermediate and slow/non-responders. Based on the magnitude of the immune response (anti-HBs titre) on day 395, the vaccinees could be divided into high (> or = 2000 U l-1) and low (< or = 2000 U l-1) responders. A close correlation between the kinetics and the magnitude of the humoral immune response was observed. The in vivo anti-HBs response was measured using commercially available immunoradiometric assays. The in vitro cellular immune response was measured using an HBsAg-specific lymphoproliferation assay. Because of interassay variability the results were considered as dichotomous variables (proliferation versus non-proliferation) for further data analysis. A statistically significant correlation was observed between the kinetics and magnitude of the humoral immune response on the one hand and the in vitro anti-HBs response on the other hand.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Expansion of circulating gamma delta T cells in active sarcoidosis closely correlates with defects in cellular immunity.

The relationship between the level of gamma delta T cells and cellular immunity of T lymphocytes was assessed in the peripheral blood of active sarcoidosis patients and healthy controls. We divided the active sarcoidosis patients into two groups: a group of patients with a normal distribution of circulating gamma delta T cells (group A; n = 11, less than 8.2% lymphocytes) and another group with increased gamma delta T cell levels (group B; n = 11, greater than 8.2% lymphocytes). The proportion and absolute count of CD4+ lymphocytes in group B (28.6 +/- 11.2%, 374.1 +/- 193.8/microliters) were remarkably smaller than control subjects (45.7 +/- 6.8%, 818.3 +/- 290.2/microliters, P < 0.001, P < 0.002, respectively). Group A, however, showed a moderate reduction in CD4+ lymphocytes when compared with controls. Serial measurements of T cell subtypes were performed on five patients in group B. gamma delta T cells and CD4+ lymphocytes were inversely correlated over the observation period which ranged from 2 to 18 months. When peripheral blood T cells were stimulated with PHA or PPD in vitro, the responses were weaker in group B compared with both group A and control subjects. These results suggest that the increase in circulating gamma delta T cells in sarcoidosis closely relates to a defect in cellular immunity which progresses during the disease process.

Adult↗

The effect of dehydroepiandrosterone on hemorrhage-induced suppression of cellular immune function.

OBJECTIVE: To determine whether the steroid hormone dehydroepiandrosterone (DHEA) improves cellular immune functions after hemorrhagic shock. DESIGN AND SETTING: Prospective controlled study in a research laboratory at an university medical center. SUBJECTS: Male NMRI mice. INTERVENTIONS: Animals received 0.9% saline or DHEA (20 mg/kg subcutaneously) before induction of a volume-controlled hemorrhagic shock (55% of estimated circulating blood volume) by retro-orbital puncture. One hour after hemorrhage mice underwent fluid resuscitation by intravenous infusion of lactated Ringer's solution (300% of the shed blood). Separate groups of mice were killed to obtain whole blood and spleen 1 h after hemorrhage, 1 h after fluid resuscitation, and 24 h after hemorrhage to determine lymphocyte distribution (CD4(+), CD8(+), NK1.1-AG(+)), splenocyte apoptosis, and plasma concentrations of tumor necrosis factor-alpha and interleukin-10. MEASUREMENTS AND RESULTS: Hemorrhage in control mice was associated with a rapid increase in circulating NK cell numbers. Elevated splenocyte apoptosis, an increased CD4/CD8 ratio, and decreased number of circulating CD8(+) T-cells was observed 24 h after hemorrhagic shock. DHEA administration was accompanied by a normalization of splenocyte apoptosis and lymphocyte migration. Induction of hemorrhagic shock did not affect TNF-alpha or IL-10 plasma concentrations in either treatment group. CONCLUSIONS: DHEA administration improves cellular immune function after hemorrhage and may therefore be beneficial in patients with hemorrhagic shock.

Animals↗

[Cellular immune responses specific for CD8+ T cell epitopes delivered by attenuated Salmonella typhimurium].

AIM: To investigate cellular immune responses against CD8(+) T cell epitopes delivered by attenuated Salmonella. METHODS: Prokaryotic expression plasmid ptG2F, carrying the oligonucleotide fragment encoding CD8(+) T cell epitope of OVA 257-264aa and LCMV NP 118-132aa fused with GFP gene was constructed and electro-transformed into the attenuated strain SL7207 of Salmonella typhimurium. The recombinant bacteria, named as SL7207(ptG2F), were screened out. C57BL/6 and BALB/c mice were immunized intravenously with SL7207(ptG2F) at two weeks intervals. Murine IFN-gamma and IL-4 secreting cells were detected in murine splenocytes after second and third immunization by Enzyme-linked immunospot assay (ELISPOT). RESULTS: The recombinant bacteria SL7207(ptG2F) induced cellular immune responses. When OVA CD8(+) T cell epitope was presented by the recombinant bacteria, the immune responses were biased toward Th1 response after second immunization and then switched to the Th1 and Th2 balance after third immunization. In contrast, when the LCMV NP CD8(+) T cell epitope was presented, the level of Th2 immune response was higher than that of Th1 after both second and third immunization. CONCLUSION: Attenuated Salmonella can effectively deliver the CD8(+) T cell epitopes and induce specific cellular immune responses. The results provide useful information for developing attenuated bacteria as novel vectors.

Animals↗

Augmentation of cellular immunity and reduction of influenza virus titer in aged mice fed Lactobacillus casei strain Shirota.

We investigated whether oral administration of Lactobacillus casei strain Shirota activates the cellular immune system and ameliorates influenza virus (IFV) titer in the nasal site in upper respiratory IFV infection by using aged mice. Natural killer activity of splenocytes and lung cells of aged mice fed an L. casei strain Shirota diet (L.casei strain Shirota group) was significantly (P < 0.01 and P < 0.05) increased compared to those fed a control diet (control group). The increases were 1.5- and 2.5-fold, respectively. In aged mice fed an XL.casei strain Shirota diet, potent induction of gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha), which play a very important role in excluding IFV, was evident in nasal lymphocytes. IFN-gamma and TNF-alpha production increased 12- and 3.5-fold, respectively. In this model of upper respiratory IFV infection, the titer of IFV in the nasal washings of aged mice fed an L.casei strain Shirota diet was significantly (P < 0.05) lower than that in aged mice fed a control diet (10(1.6 +/- 0.6) and 10(2.2 +/- 0.5), respectively). These findings suggest that oral administration of L.casei strain Shirota activates not only systemic cellular immunity but also local cellular immunity and that it ameliorates IFV infection.

Administration, Oral↗

[Effect of cefodizime on cellular immunity in patients with lung cancer].

OBJECTIVE: To study the enhancing effect of cefodizime on cellular immunity of patients with lung cancer. METHODS: The parameters of cellular immunity in blood and pulmonary alveoli were investigated in 45 patients with lung cancer complicated with lower respiratory tract infection (LRTI) and 10 non-cancer patients with LRTI. Nitroblue tetrazolium (NBT) reaction of polymorphonuclear neutrophils (PMN), the percentage of natural killer (NK) cells, and that of CD4+ cells, ratio of CD4+/CD8+ in peripheral blood, OD value of alveolar macrophages phagocyting neutral red, and IL-1 beta (ng/L) in broncho-alveolar lavage flind (BALF) were determined. RESULTS: The parameters examined in cancer patients with LRTI were significantly improved after cefodizime treatment, approaching to those seen in non-cancer patients with LRTI. The therapeutic results were better in patients treated with cifodizime than in patients treated with ceftriaxonum. CONCLUSION: Cefodizime is a better choice of antibiotic for the treatment of lung cancer complicated with lower respiratory tract infection. Its enhancing effect on systemic and local immune functions plays a role.

Adult↗

Cellular immunity induced by lung immunization of Fischer 344 rats.

This study describes immunologic response in lung-associated lymph nodes, spleen, cervical lymph nodes and lung lavage cells of rats immunized by intratracheal instillation of BCG-sheep red blood cell (SRBC) suspensions. At 4 through 17 days after immunization, the number of anti-SRBC IfM and IgG antibody-forming cells was significantly increased only in the lung-associated lymph nodes, indicating that these tissues retain the particulate antigen that was deposited in the lung. In contrast, cellular immunity was found initially in the spleen, with significant responses in the lungs and in the lung-associated lymph nodes on 13--19 days after immunization. Our data indicated that the lung-associated lymph nodes are probably the initial site for the production of antigen-sensitive lymphocytes for both antibody and cellular immunity after lung immunization. Cells responsible for cellular immunity appear to migrate to the spleen, where further cell division take place.

Animals↗

Cellular immune responses to HIV.

The cellular immune response to the human immunodeficiency virus, mediated by T lymphocytes, seems strong but fails to control the infection completely. In most virus infections, T cells either eliminate the virus or suppress it indefinitely as a harmless, persisting infection. But the human immunodeficiency virus undermines this control by infecting key immune cells, thereby impairing the response of both the infected CD4+ T cells and the uninfected CD8+ T cells. The failure of the latter to function efficiently facilitates the escape of virus from immune control and the collapse of the whole immune system.

AIDS Vaccines↗

[Cellular immunity in protein-caloric malnutrition].

In order to have a clearer idea on the relationship between infectious diseases and malnutrition, cellular immunity is studied in 3 to 18 months old malnourished and healthy infants. Nutritional status is evaluated by the food intake the anthropologic measurements and some biological parameters like transferrin. Cellular immunity is investigated by skin tests to tuberculin, monilia, P.H.A. and DNCB. Absolute number of peripheral lymphocytes and percentage of T cells are studied too. The results show that there is a cellular immunity deficiency: frequent non-response to antigens, weak sensitization to DNCB. Some patients have a low percentage of spontaneous rosettes. The transferrin titering is useful to appreciate the nutritional status and the iron therapy opportunity, the prognostic and the immunitary possibilities.

Candida↗

Intraspleen DNA inoculation elicits protective cellular immune responses.

DNA immunization or inoculation is a recent vaccination method that induces both humoral and cellular immune responses in a range of hosts. Independent of the route or site of vaccination, the transfer of antigen-presenting cells (APC) or antigens into lymphoid organs is necessary. The aim of this investigation was to test whether intraspleen (i.s.) DNA inoculation is capable of inducing a protective immune response. We immunized mice by a single i.s. injection of a DNA construct expressing the immunoglobulin (Ig) heavy-chain variable domain (VH) in which the complementarity-determining regions (CDR) had been replaced by a Taenia crassiceps T-cell epitope. In these mice, immune responses and protective effects elicited by the vaccine were measured. We have shown here for the first time that i.s. DNA inoculation can induce protective cellular immune responses and activate CD8(+) T cells. Also, Ig V(H) appeared to be the minimal delivery unit of "antigenized" Ig capable of inducing T-cell activation in a lymphoid organ. The strategy of introducing T-cell epitopes into the molecular context of the V(H) domain in combination with i.s. DNA immunization could have important implications and applications for human immunotherapy.

Animals↗

Cellular immunity in lepromatous and tuberculoid leprosy.

The depression of cellular immunity in lepromatous patients is not understood. While the blood monocytes of leprosy patients appear to be activated normally by lymphokines, T cell proliferation and production of lymphokines in response to Mycobacterium leprae are impaired in lepromatous patients. Attempts to restore responsiveness in cells from these patients have been unsuccessful in our hands. The addition of exogenous IL-2 to leukocyte cultures does not appear to restore responsiveness to M. leprae in cells from nonresponder patients. Rather, some enhancement, often not antigen specific, is observed in cells from patients with a preexisting response. Similarly, depletion of monocytes does not restore responsiveness to M. leprae in non-responder patients, but a nonspecific enhancement of proliferation is observed in monocyte-free cultures from patients that do respond to M. leprae. Thus, the defect in lepromatous non-responder patients does not result from a simple lack of IL-2 production or suppression by monocytes and/or their products. Possibly, there is a low level or lack of M. leprae responsive T cells in the circulation of these patients.

Humans↗

Rotavirus-specific humoral and cellular immune response after primary, symptomatic infection.

The humoral and cellular immune response after symptomatic, primary rotavirus infection was examined in 8 children < 2 years old. Rotavirus-specific IgA, rotavirus-specific helper T (Th) cells, and neutralizing antibody responses were evaluated at the time of illness, 2-8 weeks later, and 3-5 months later. In addition, rotavirus strains associated with infection were tested by polymerase chain reaction analysis using oligonucleotide primers specific for genes 4 (P type) and 9 (G type). The absence of rotavirus-specific IgA or rotavirus-specific helper T cell activity at the time of illness was consistent with a primary infection in 7 of 8 children. Two children were infected with serotype 1 (P type 1, G type 1), 3 with serotype 3 (P type 1, G type 3), and 3 with serotype 4 (P type 1, G type 4) strains. Neutralizing antibodies were directed against the gene 4 (P type) protein product (vp4). Because all infecting strains were P type 1, convalescent antisera did not distinguish among different rotavirus G types. Rotavirus-specific IgA responses were detected in 6 of 8 and rotavirus-specific Th cell responses in 7 of 8 children during convalescence.

Acute Disease↗