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Nonimmune rosette formation: a measure of the newborn infant's cellular immune response.

Nonimmune rosette formation, an in vitro measure of cellular immunity, was evaluated in normal newborn infants. Active rosette formation in 14 specimens of cord blood was 18.9 +/- 4.8% compared to 28.1 +/- 5.2% in 15 adult control samples (p less than 0.05). Total rosette formation in 13 cord blood samples was 33.3 +/- 7.6% compared to 55.1 +/- 6.5% in 15 adult control specimens (p less than 0.05). Tritiated thymidine uptake from phytohemagglutinin stimulation was comparable in cord blood and adult control lymphocytes. The importance of these findings is discussed in light of other recent reports suggesting that cord blood thymic derived T lymphocytes may have reduced immune capability when compared to adult lymphocytes.

Fetal Blood↗

Unspecific cellular immunity before therapy in patients with squamous cell carcinoma of head and neck.

An introduction to the role of lymphocytes in immunological reactions is given. Two fundamental categories of immunological response are described which are mediated by two distinct subpopulations of lymphocytes: B-lymphocytes are responsible for humoral immune reactions and T-lymphocytes are involved in cell-mediated immunity. Information is given on the role of the immune system in generation of anti-tumour activities and of mechanisms leading to an acceleration of tumour growth. Several pathways of cytotoxic and blocking reactions against target cells are mentioned. Furthermore, methods are described for monitoring the non-specific immune reactivity of the host. These nonspecific cellular immune responses in 30 patients with squamous cell carcinoma of the head and neck were compared with those in 30 healthy controls. Assays were performed in vitro to evaluate the blastogenic response of lymphocytes to the mitogens PHA (phytohaemagglutinin) and PWM (pokeweed mitogen) and to quantify T-rosetteforming lymphocytes in the peripheral blood. The in vivo assays used were the delayed cutaneous hypersensitivity reaction to the primary stimulus of DNCB (dinitro-chloro-benzene) and the recall reaction to PPD (purified protein derivate). The carcinoma patients demonstrated significant impairment of lymphocyte blastogenesis reactions to PHA but not to PWM. The percentage and absolute counts of T-rosettes was significantly reduced in cancer patients compared with normal controls. Skin test reactivity to de-novo sensitation with DNCB was significantly abnormal in patients with head and neck cancer. However, delayed type hypersensitivity evaluated with PPD (recall antigen) was not significantly reduced. After subdividing the cancer patients according to their clinical stage of disease and subsequent analysis, they showed no correlation between clinical stage and immune reactivity. These data indicate that PHA induced lymphocyte blastogenesis, enumeration of T-rosette levels and evaluation of delayed hypersensitivity reaction to DNCB are potentially useful for the study of squamous cell carcinoma of head and neck to monitor effects of tumour treatment and perhaps to evaluate a correlation between immunocompetence and prognosis.

Adult↗

The murine cellular immune response to adenovirus type 5.

We have characterized the cellular immune response to human adenovirus 5 (Ad-5) in mice, as a basis for future study of responses to foreign antigens in recombinant adenoviruses. Primary in vivo lytic effector cells contained both virus immune cytolytic T (Tc) cells and natural killer cells. The Tc effectors could be boosted in vitro to give a secondary Tc cell response. The Tc cell response to Ad-5 was major histocompatibility complex (MHC) restricted, and in CBA/H (H-2k) mice mapped to the K end of MHC. Kinetic experiments suggested the Tc cell response was directed against early rather than late viral proteins. Experiments with viral mutants showed that the main responses were to the E1A and E1B proteins, with some involvement of E2. Expression of E3 and E4 in infected targets was not required, in fact lysis of target cells infected by viruses with a deletion in E3 was augmented.

Adenoviruses, Human↗

Cellular immunity to viral and fungal antigens after stem cell transplantation.

Cellular immunity to viral and fungal antigens is often suppressed after stem cell transplantation. Viral infections, in particular infections with cytomegalovirus and Epstein-Barr virus, are often reactivated after allogeneic stem cell transplantation. Pathogenetic factors are immune deficiency and T-cell stimulation in the course of graft-versus-host reactions. Fungal infections are opportunistic infections derived with ubiquitous microorganisms. Immune deficiency, neutropenia, steroid treatment, and antibiotic treatment contribute to the pathogenesis. The study of viral and fungal immunity after allogeneic stem cell transplantation gives insight into the reconstitution of the immune system and tolerance.

Antigens, Fungal↗

Peri-operative modulation of cellular immunity in patients with colorectal cancer.

The peri-operative cellular immune response is depressed in patients with gastrointestinal cancer, a factor which may facilitate malignant dissemination. We have investigated the effects of peri-operative rIL-2 and a combination of rIL-2 and interferon-alpha (IFN-alpha) on both peripheral blood lymphocyte function and number in patients undergoing surgical resection for colorectal cancer. Fifty-two patients were randomly allocated to either control, rIL-2 or rIL-2 with IFN-alpha treatment arms. In vitro studies were performed pre-operatively and on post-operative days 1, 4, 7 and 10. Natural killer (NK) and lymphokine-activated killer (LAK) cell function were profoundly depressed in control patients (P < 0.001; P < 0.01), an effect abrogated in both treatment groups; indeed NK function was augmented in the rIL-2 and IFN-alpha group on the first post-operative day in association with an increase in the percentage of cells expressing CD16 and CD56 (P < 0.01). Flow cytometric analysis of lymphocyte subsets in the control group was unremarkable, except for an early post-operative fall in numbers of lymphocytes. Treatment with either rIL-2 or rIL-2 and IFN-alpha produced an initial profound reduction in T lymphocyte numbers, followed by a 'rebound' lymphocytosis of activated CD3+ T cells, as demonstrated by a significant increase in co-expression of CD25, CD38 and CD45RO. No significant differences were observed between either of the treatment groups. Adjuvant immunotherapy affects peri-operative anti-tumour immune responses, and this may influence long term outcome in patients undergoing surgery for gastrointestinal cancer.

Colorectal Neoplasms↗

Restoration of cellular immune response by levamisole in patients with Hodgkin's disease.

Cellular responses were studied in patients with Hodgkin's disease before and after levamisole treatment "in vivo" by measuring delayed skin reactivity to various antigens (PPD, Mumps, Candida and SK-SD), and "in vitro" by evaluating lymphocyte capacity to form spontaneous rosettes and to react to the T-cell mitogen PHA. Levamisole was found to significantly increase both the delayed skin reactivity and the number of T-rosette forming lymphocytes. Patients within two years from irradiation had reduced reactivity to PHA and in them levamisole significantly increased this reactivity. On the other hand, patients who had been irradiated more than two years prior to the study had normal reactivity to PHA which tended to decrease under levamisole treatment. It is concluded that levamisole restores the depressed cellular immunity in patients with Hodgkin's disease and its administration might be indicated in patients, especially in the immediate post-irradiation period.

Hodgkin Disease↗

A study of cellular immunity in newborns after prevention of respiratory distress syndrome (RDS).

Cellular immune responsiveness against infections was evaluated in four groups of newborns. The first group was composed of preterm newborns whose mothers had received betamethasone for prevention of RDS, the second group of preterm newborns whose mothers had received ambroxol for prevention of RDS, the third group of preterm newborns whose mothers had not received any drug enhancing surfactant production, and the fourth group were healthy-term infants. A reduction of OKT4+ cells and functional deficits of neutrophils were found in preterm infants born to mothers treated with steroids, whereas no functional abnormalities of immune-competent cells were observed in preterm infants born to mothers treated with ambroxol.

Ambroxol↗

[Therapy with transfer factor in diseases with disorders of the cellular immune reaction].

On the basis of publications on experimental therapy with transfer factor is tried to show limits and perspective of a new therapeutic principle. The now 10-year-old therapeutic experiences with dialysates of leucocytes and chromatographically cleansed fractions were confirmed by the new investigations of the last years which were evaluated. They show the transfer factor as an effective immune therapeutic for the stimulation of the cellular immunity in a large number of diseases. In these cases a combination with other therapeutic measures proved particularly favourable. Concerning the breadth of use and the chances of success chronic infections are in the foreground. A practical importance of the transfer factor for the treatment of malignant diseases is at present not to be seen. Comprehensive double blind studies with large groups of patients are further necessary, in order to exclude accidental findings for the corresponding picture of the disease and to estimate possible chances of success.

Humans↗

Modulation of the cellular immune responses to T-cell-dependent and T cell-independent antigens in lambs with induced bovine viral diarrhea virus infection.

Functional interaction between lymphoid cells and lymphotropic viruses is particularly evident for bovine viral diarrhea virus (BVDV) in cattle and its closely related virus, the border disease virus (BVDV) in sheep. The most important aspect of acute or chronic phases of BVDV or BDV infection was the host's increased susceptibility to secondary bacterial or viral infection. To study the ability of BVDV to alter the development of the cellular immune responses to concomitant inoculation with T cell-dependent and T cell-independent antigens, lambs were inoculated twice with rabbit RBC and Escherichia coli lipopolysacharide (LPS) and then were infected with a cytopathic strain of BVDV at postinoculation day 3. Leukopenia characterized by lymphopenia developed after BVDV infection. Increased [3H]thymidine incorporation was observed in resting or lectin-stimulated blood mononuclear cells in the first weeks after inoculation in BVDV-infected lambs, but was followed by decreased [3H]thymidine incorporation after the second inoculation for up to 8 weeks after initial inoculation. In contrast, transient decrease of blastogenic responses, associated with toxic effect of LPS, was detected in inoculated noninfected lambs, but was followed by stimulation of cellular immune responses. Inoculated noninfected lambs had good in vitro cellular immune response to rabbit RBC and LPS antigens, whereas lymphocytes from BVDV-infected lambs could not mount lasting cellular immune responses to antigens or BVDV. Results suggest that BVDV infection in lambs modulates the ability of lymphocytes to respond to lectins or antigenic stimuli according to the time after infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mycobacterium fortuitum pulmonary infection associated with an antigen-selective defect in cellular immunity.

In this study we describe the first example of a well documented case of pulmonary infection caused by Mycobacterium fortuitum shown to be associated with an antigen-selective defect in cell-mediated immunity to this organism. Immunologic parameters were evaluated before, during and after antibiotic treatment with amikacin. A defect in cellular immunity to purified protein derivative from Myco. fortuitum, shown to be antigen-selective as indicated by normal responsiveness to purified protein derivative from Mycobacterium tuberculosis and several other common recall antigens, accompanied the prolonged infection by this organism. During the first three months of treatment with amikacin, the patient's clinical status improved coincident with the eradication of the organism from the sputum. During the next three months of therapy with amikacin, however, a generalized defect in cellular immunity developed, and the lung disease again progressed. The deteriorating clinical condition was presumably related to a generalized cellular immune anergy or hyporesponsiveness induced by the amikacin therapy. After three more months of treatment, the organism became resistant to the drug and reappeared in sputum cultures. Since amikacin therapy was discontinued, the patient's general immune responsiveness returned to normal. He did, however, remain unresponsive to purified protein derivative from Mycobacterium fortuitum.

Amikacin↗

Effects of one year of supplementation with zinc and other micronutrients on cellular immunity in the elderly.

The objective of this study was to determine the effects of a year of Zn supplementation on Zn concentrations in circulating cells and on cellular immune functions in the elderly. Subjects, aged 60-89, were given a placebo, 15 mg Zn, or 100 mg Zn daily for 12 months. All subjects also received a multivitamin/mineral supplement that contained no additional Zn. Blood samples were drawn and immune functions assessed prior to and at 3, 6, 12, and 16 months after beginning Zn supplementation. Subject diets were also assessed at each visit. Dietary folate, pyridoxine, alpha-tocopherol, copper, zinc, and magnesium were consistently below recommended intakes. Although plasma Zn increased significantly in the 100 mg Zn treatment group, concentrations of Zn in erythrocytes, mononuclear cells, polymorphonuclear leukocytes, and platelets were not significantly increased by zinc supplementation. Natural killer cell activity was transiently enhanced by the 100 mg/day dose of Zn. There was a progressive improvement in delayed dermal hypersensitivity (DDH) and in lymphocyte proliferative responses to two mitogens; this may have been due to one or more components of the multivitamin/mineral supplement administered to all study subjects. The enhancement of DDH was significantly greater in the placebo group than in either zinc treatment group. Thus, zinc had a beneficial effect on one measure of cellular immune function while simultaneously having an adverse effect on another measure of cellular immunity.

Aged↗

Effects of beta-glucan extracted from Saccharomyces cerevisiae on humoral and cellular immunity in weaned piglets.

Twenty-four barrows were used to investigate the effects of beta-glucan on immune function in weaned piglets. Pigs (8.09 +/- 0.20 kg, 28 d of age) were fed a diet without or with supplemented beta-glucan (50 mg/kg feed). All pigs were injected with ovalbumin (OVA) on day 14 to investigate their humoral immune response. On day 28, lymphocytes were isolated from all pigs to determine the effects of beta-glucan on cellular immunity of pigs in vitro. Lymphocytes from six pigs of each group were incubated with 16 microg lipopolysaccharide (LPS) per ml culture medium, the remainder with an equivalent volume of culture medium alone. Samples were collected at 0, 3, 6, 12, 18, 24, and 48 h after LPS addition for determination of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interleukin-10 (IL-10). On day 31, six pigs of each group were injected with either LPS (25 microg/kg BW) or an equivalent amount of sterile saline. Blood samples were collected at 3 h after LPS injection for analysis of IL-6, TNF-alpha, and IL-10 in plasma. The results indicated that dietary beta-glucan enhanced pig antibody response to OVA only in the first week after injection. In vitro, the increases of IL-6 and TNF-alpha in culture medium were partially dampened in pigs supplemented with beta-glucan when their lymphocytes were incubated with LPS, whereas the increase of IL-10 was potentiated. In vivo, dietary beta-glucan attenuated the increase of plasma IL-6 and TNF-alpha, and enhanced the increase of plasma IL-10 when pigs were challenged with LPS. These results demonstrate that beta-glucan can improve the humoral immunity of pigs and modulate cellular immunity of pigs by mitigating the elevation of pro-inflammatory cytokines and enhancing the increase of anti-inflammatory cytokines after an immunological challenge.

Animal Feed↗

Patterns of cellular immune responses to thyrocyte membrane antigens and specific immunoregulatory defects in autoimmune thyroid disease.

Although Graves' disease (GD), Hashimoto's thyroiditis (HT) and idiopathic myxoedema (Myx) are clinically distinct autoimmune thyroid diseases, previous studies using crude thyroid preparations as a source of antigens have failed to identify differences in cellular immune responses. In this study, we have assessed cellular immunity in patients with these disorders to two antigen preparations (derived from thyroid gland and cervical fat) enriched in cell membranes and known to share a functional TSH receptor. Using an indirect T-lymphocyte migration inhibitory factor (T-LIF) assay, T-cell immunity to thyroid membranes was demonstrated in 11/11 patients with GD, 4/5 with HT and 4/5 with Myx, but in none of 18 patients with chronic active hepatitis (another organ-specific autoimmune disease) or sixteen healthy controls. In contrast, T lymphocytes responsive to adipocyte membranes were detected only in patients with GD. TSH binding inhibiting antibodies were found exclusively in six patients with GD, and thyroid stimulating antibodies in five of these patients. In co-culture experiments designed to study the activity of antigen-specific suppressor T cells, low numbers of T cells from 6/6 normal controls, 4/4 patients with HT and 5/5 patients with myxoedema suppressed the response to adipocyte membranes of T lymphocytes from patients with Graves' disease. The results of this study demonstrate different patterns of T-cell reactivity to thyroid antigens in patients with Graves' disease, Hashimoto's thyroiditis and myxoedema and suggest that cellular immunity to the TSH receptor is restricted to patients with Graves' disease and associated with a defect in the specific immunoregulatory control of this response.

Adolescent↗

[Cellular immunity factors in the pathogenesis of recurrences of chronic herpetic infection].

Comparative studies of various factors of cellular immunity in human chronic herpetic stomatitis (CHS) in periods of relapses and remission of the infection revealed no significant changes in specific cellular immune response, blasttransformation of lymphocytes to herpes simplex virus antigen. At the same time, the indices of nonspecific cellular responsiveness: the rosette-forming activity of T-lymphocytes and the level of leukocyte interferon were markedly reduced in the period of recurrence of the infection and increased as remission developed. The role of immune factors in the pathogenesis of herpes relapses is discussed.

Adolescent↗

Comparison of the kinetics of the specific cellular immune response to duck hepatitis B virus in infected and immune ducks.

The kinetics of the cell mediated immune response by ducks acutely and chronically infected with, or immune to infection by duck hepatitis B virus (DHBV) was determined. This was measured by an antigen specific blastogenesis assay to duck hepatitis B surface antigen (DHBsAg) and duck hepatitis B core antigen (DHBcAg) using peripheral blood mononuclear cells (PBMC). The three outcomes of acute infection by DHBV were either clearance from both serum and liver, clearance from serum but not liver, or the development of persistent viraemia. Acutely infected ducks that failed to clear the infection also failed to develop a significant cellular immune response to both antigens. Ducks with chronic infection acquired as neonates or as the result of the failure to clear acute infection had an increasing cellular immune response over time. Two groups of immune ducks were examined. These were either ducks that had become immune following infection or that had been vaccinated. Both groups of ducks demonstrated significant cellular responses following challenge with DHBV irrespective of the level of their responses before challenge. However, there was a reduction in the response of their PBMC over a 4-week-period postchallenge. The range of cellular immune responses to DHBV antigens observed in this study has a number of counterparts in hepatitis B infection of humans. Coupled with the defined clinical outcomes that can be established in the duck/DHBV model, further study of the cellular immune response to DHBV is warranted.

Animals↗

The relationship of abnormalities of cellular immunity to antibodies to HTLV-III in homosexual men.

A comprehensive evaluation of the cellular immune system (total T-cell, helper cell, suppressor cell, and natural killer cell numbers; in vitro interleukin-2 production, T-cell responses to mitogens and antigens, serum beta 2 microglobulin levels, and delayed hypersensitivity skin tests) was performed on 36 HTLV-III seronegative and 16 HTLV-III seropositive healthy homosexual men, 48 asymptomatic homosexual men with the chronic lymphadenopathy syndrome, 41 patients with AIDS, and 29 heterosexual controls without any known risk factors for AIDS. Our studies demonstrate that HTLV-III seronegative homosexual men have normal cellular immunity and are comparable to heterosexual controls. The abnormalities of lymphocyte subsets observed in HTLV-III seropositive healthy homosexual men are comparable to subjects with chronic lymphadenopathy. Assays of lymphocyte function, with the exception of delayed type hypersensitivity (DTH) skin tests, are similar in each group except patients with AIDS. Subjects with chronic lymphadenopathy were less responsive to DTH skin tests and HTLV-III seropositive healthy homosexuals were comparable to chronic lymphadenopathy subjects. We conclude that immunologic abnormalities in homosexual men are attributable to infection with HTLV-III.

Acquired Immunodeficiency Syndrome↗

Vaccines against intracellular infections requiring cellular immunity.

Vaccines against a variety of infectious diseases represent one of the great triumphs of medicine. The immune correlates of protection induced by most current vaccines seem to be mediated by long-lived humoral immune responses. By contrast, there are no currently available vaccines that are uniformly effective for diseases such as HIV, malaria and tuberculosis, in which the cellular immune response might be crucial in mediating protection. Here we examine the mechanisms by which long-lived cellular immune responses are generated and maintained in vivo. We then discuss current approaches for vaccination against diseases in which cellular immune responses are important for protection.

Animals↗