Decrease In Lymphocyte Response Research Articles

Lymphocyte proliferation in response to acute heavy resistance exercise in women: influence of muscle strength and total work.

Little is understood about the immune responses to heavy resistance exercise. The purpose of this investigation was to determine the influence of physical strength and the ability to do more total work on lymphocyte proliferation after an acute bout of heavy resistance exercise. A group of 50 healthy but nonstrength trained women were recruited for the study and tested for their one repetition maximum (i.e. 1 RM or maximal mass lifted once). From the normal distribution of strength the top and bottom 8 women [mean age 22.5 (SD 3.1) years] were asked to volunteer to define our two groups (i.e. high strength and low strength). The two groups were significantly different (P < 0.05) in 1 RM squat strength [low strength 39.9 (SD 4.6) kg, 0.65 (SD 0.08) kg.kg body mass-1 and high strength 72.2 (SD 10.7) kg, 1.1 (SD 0.12) kg.kg body mass-1] but were not significantly different in body mass, age, activity levels, and menstrual status (all in same phase). Each performed a resistance exercise protocol consisting of six sets of 10 RM squats with 2 min rest between the sets. The 10 RM loads and total work were significantly greater in the high strength group than in the low strength group. Blood samples were obtained pre-exercise and immediately post-exercise for test for lactate (significant increase with exercise) and cortisol (no changes) concentrations with no differences noted between groups. Immunological assays on the blood samples determined the incorporation of tritiated thymidine by lymphocytes in responses to concanavalin A (ConA), phytohemagglutinin (PHA), and pokeweed mitogen (PWM). Following the squat exercise, there was a significant decrease in lymphocyte responsiveness to PWM in the high strength but not in the low strength group for both total proliferation and proliferation adjusted per B or T cell. On the other hand, lymphocytes from the low strength group proliferated to a significantly greater extent (adjusted per T cell) in response to ConA and PHA. These data indicate that the heavy resistance exercise protocol reduced the lymphocyte proliferative responses only in the stronger group of subjects. This effect may have been due to the high absolute total work and the greater exercise stress created by the resistance exercise protocol in the high strength group. Therefore, individuals performing at the same relative exercise intensity (i.e. 10 RM) in a resistance exercise protocol may have different immune responses stemming from differences in absolute total work performance.

The role of cell-mediated immunity in the pathogenesis of bluetongue virus serotype 11 in the experimental infection of vaccine/sensitized calves

The cellular immune response of cattle to virulent and avirulent (inactivated) bluetongue virus (BTV) was studied. Each of three calves received three vaccinations (sensitizations) with binary ethyleneimine (BEI)-inactivated BTV, 3 weeks apart. The sensitized animals were challenged with BTV-11 strain UC8 3 weeks after the last vaccination. BTV-seropositive and BTV-seronegative calves were used as controls. The animals were bled weekly for virus isolation and for evidence of cell-mediated immunity (CMI) as determined by the lymphocyte stimulation test (LST). Peripheral blood mononuclear leukocytes (PBML) cultures were induced with purified BTV antigen; the phytomitogens phytohemagglutinin (PHA), Concanavalin A (ConA) and pokeweed (PKW) mitogen, and combinations of phytomitogens and BTV antigen. LST data were analysed by ANOVA and reported as counts per minute (CPM) and stimulation index (SI). Following BTV challenge exposure, significant SI to mitogens were found in PBML cultures for all animals. BTV antigen induced a weak CMI response. There was evidence of perturbations in lymphocyte response as characterised by a sharp decrease in lymphocyte response to mitogens following combined BTV-antigen and mitogen PBML induction. The SI diminished in PBML cultures after a 4 day incubation period, except for ConA. These results provide evidence that the cell-mediated immune response could be affected by BTV and that inhibitory mediators might play an important role in the pathogenesis of BTV in cattle.

Selenium status and immune function in asymptomatic HIV-1 seropositive men

Altered selenium status has been shown to be associated with impairment of immune function. The present study was conducted to characterize selenium status in HIV-1 infected individuals (n=70), and determine whether alterations in selenium status were related to immune system dysregulation. Sixty-six percent of HIV-1 seropositive homosexuals, healthy other than persistent generalized lymphadenopathy, exhibited normal plasma selenium levels (85–120 μg/L). In contrast, 23% of such HIV-1 seropositive individuals had high (>120 μg/L) and 11% had low (<85 μg/L) plasma selenium levels. Normal selenium levels appear to be optimal for maintaining immune function. Low selenium levels were associated with a reduced natural killer cytotoxic activity. On the other hand, HIV-1 infected individuals who had high levels of selenium demonstrated significantly lower levels of immunoglobulins (IgG and IgM) and a marked decrease in lymphocyte response to plant lectin phytohemagglutinin (PHA), as compared to the normal and low selenium level groups. No relationship between selenium levels and CD4, CD8 cell numbers or their ratios was observed. These data suggest that individuals with early HIV-1 infection frequently have abnormal selenium status, with both high and low selenium levels observed, and that altered plasma selenium levels, were associated with additional immune dysregulation.4

Measurement of lymphoblastogenic activity from thorium workers.

Mitogenic stimulation of peripheral blood lymphocyte cultures obtained from 36 thorium workers was studied to determine whether the response of these cells was affected by the individuals' occupational exposure to alpha irradiation. The standard assay involved incubating 2 X 10(5) lymphocytes per test well for 72 hours in the presence of phytohemagglutinin (PHA), concanavalin A (Con A) or pokeweed mitogen (PWM). The results showed that there was a significant decrease in lymphocyte responsiveness of former thorium workers grouped by decade of life when compared with controls of the same decade of life for each mitogen tested with the exceptions of PHA in the 41-50 age group and PWM in the 51-60 age group. We are unable to correlate the decreased response observed with the measured body burdens, external gamma exposure, or thoron exhalation rates in these thorium cases. However, other occupational exposures (i.e., various chemicals used in processing thorium) cannot be eliminated as a possible cause.

Animal model for immune dysfunction associated with adenosine deaminase deficiency.

An in vivo murine model for immunodeficiency of both B and T cells is produced by continuous intraperitoneal infusion of 2'-deoxycoformycin (DCF), a specific tightly binding inhibitor of adenosine deaminase (ADase; adenosine aminohydrolase, EC 3.5.4.4). After DCF infusion, ADase of thymus, spleen, and lymph nodes was inhibited to varying degrees ranging from 57% to 100%. Immunodeficiency under these conditions was indicated by: (i) a striking decrease in lymphocyte response to the T-cell mitogens concanavalin A and phytohemagglutinin; (ii) an impairment of delayed hypersensitivity measured by the footpad reaction; (iii) a decrease in antibody production measured in both in vivo and in vitro plaque-forming cell assay; (iv) a significant prolongation of mouse skin allograft survival after transplantation into the C57BL/6J (H-2b) strain of skin from BALB/c (H-2d) mice; and (v) a marked lymphopenia. Histological examination indicated lymphoid degeneration in the thymus, lymph nodes, and spleen with no alterations in other tissues including bone marrow, kidney, lung, gastrointestinal tract, and liver except for the occurrence of hepatitis. A decrease in the number of Thy-1-positive cells in both spleen and lymph nodes further supported the fact of cytotoxicity of DCF to T cells. Anorexia and weight loss were observed within 5 days of continuous DCF infusion at 0.4 mg/kg body weight per day. These data indicate that this method provides an experimental model for future studies on the biochemical mechanisms responsible for the genetically determined severe combined immunodeficiency disease in man.

Immunological family studies in Hodgkin's disease. Is the immunodeficiency horizontally transmitted?

27 consanguineous and non-consanguineous relatives to 12 patients with Hodgkin's disease (HD) have been studied. The lymphocyte DNA synthesis induced by concanavalin (ConA) was depressed in 6 patients. 7 out of 15 tested relatives (3 first degree relatives and 4 spouses) showed a profound impairment in lymphocyte response to ConA stimulation. None out of 12 relatives to ConA normal patients was defect in this respect. In relatives to ConA hyporesponsive patients there was a small but statistically significant decrease in lymphocyte response to pokeweed mitogen (PWM) and PPD in vitro. No differences in lymphocyte subpopulations were seen. The findings strongly support an exogenous factory (probably a virus) causing the depressed mitogen response in relatives to immunodeficient patients with HD. A possible linkage between the immunodeficiency and the pathogenesis of HD is discussed.

Influenza in ferrets and guinea pigs: effect on cell-mediated immunity.

Two different animal models were studied to determine whether localized upper respiratory tract viral infection was associated with suppression of systemic cell-mediated immunity. During influenza infection in ferrets, there was no significant decrease in lymphocyte responsiveness to phytohemagglutinin (PHA). Guinea pigs given influenza showed no significant change in their response to PHA or to picryl human serum albumin (picHSA), to which they had been immunized previously. Delayed hypersensitivity skin test responses to picHSA in guinea pigs remained intact during infection. No change in the percentage of circulating T lymphocytes was detected during influenza infection. Transfer of immunity to nonsensitized recipient guinea pigs from picHSA-sensitized guinea pigs was accomplished during influenza infection. Lack of a suppressive effect on systemic cell-mediated immunity after influenza challenge in these two animal models of mild influenza confirmed previous findings in humans with mild influenza infection.

The effect of immunotherapy on humoral and cellular responses in ragweed hayfever.

The effect of specific immunotherapy on several in vitro responses to ragweed antigen E has been evaluated in 17 atopic patients with ragweed hayfever. The methods employed were leukocyte histamine release, measurement of specific IgE anti-ragweed antibody and specific IgG anti-ragweed antibody, lymphocyte proliferation, and the production of two lymphocyte mediators (migration inhibitory factor and mitogenic factor). The duration of treatment and symptom improvement were also recorded for comparison. Immunotherapy was associated with a decrease in leukocyte sensitivity for histamine release to ragweed antigen E in a majority of the patients. In addition, there was a significant decrease in IgE anti-ragweed antibody and a significant increase in IgG anti-ragweed antibody. Immunotherapy also resulted in a significant decrease in lymphocyte responsiveness to ragweed antigen E as measured by proliferation and the production of mediators. Symptomatic improvement was best correlated with the presence of IgG anti-ragweed antibody responses. The production of this antibody was also associated with a decrease in lymphocyte responsiveness. The results of this study indicate that specific immunotherapy in ragweed-sensitive patients induces alterations in immunologic reactivity to ragweed antigen in vitro. This response is antigen specific, includes elements of both humoral and cellular immunity, and may account for the clinical improvement that is often observed in patients who undergo this form of therapy.