Endurance Exercise Diverts the Balance between Th17 Cells and Regulatory T Cells

Endurance, marathon-type exertion is known to induce adverse changes in the immune system. Increased airway hyper-responsiveness and airway inflammation are well documented in endurance athletes and endurance exercise is considered a major risk factor for asthma in elite athletes. Yet, the mechanisms underlying this phenomenon are still to be deduced. We studied the effect of strenuous endurance exercise (marathon and half-ironman triathlon) on CD4+ lymphocyte sub-populations and on the balance between effector and regulatory CD4+ lymphocytes in the peripheral blood of trained athletes, Endurance exercise induced a significant increase in Th17 cells and a sustained decrease in peripheral blood regulatory T cells (Tregs). While interleukin (IL)-2 levels remained undetectable, post-race serum IL-6 and transforming growth factor (TGF) β levels were significantly elevated. Treg levels in sedentary controls'' decreased in vitro after incubation with athletes'' post-exercise serum, an effect that was attenuated by supplements of IL-2 or anti IL-6 neutralizing antibodies. Our data suggest that exercise-induced changes in serum cytokine levels promote alterations in Tregs and Th17 cell populations, which may divert the subtle balance in the immune system towards inflammation. This may explain allergic and autoimmune phenomena previously reported in endurance athletes and contribute to our understanding of exercise-related asthma.     

Effects of resistance training on selected indexes of immune function in elderly women.

Women aged 67-84 yr were randomly assigned to either resistance exercise (RE, n = 15) or control group (C, n = 14). RE group completed 10 wk of resistance training, whereas C group maintained normal activity. Blood samples were obtained from the RE group (at the same time points as for resting C) at rest, immediately after resistance exercise, and 2 h after exercise before (week 0) and after (week 10) training. Mononuclear cell (CD3+, CD3+CD4+, CD3+CD8+, CD19+, and CD3-CD16+CD56+) number, lymphocyte proliferative (LP) response to mitogen, natural cell-mediated cytotoxicity (NCMC), and serum cortisol levels were determined. Strength increased significantly in RE subjects (%change 8-repetition maximum = 148%). No significant group, exercise time, or training effects were found for CD3+, CD3+CD4+, or CD3+CD8+ cells, but there was a significant exercise time effect for CD3-CD16+CD56+ cells. LP response was not different between groups, across exercise time, or after training. NCMC was increased immediately after exercise for RE subjects at week 0 and for RE and C groups at week 10. The week 0 and week 10 NCMC values were above baseline for both RE and C groups 2 h after exercise. In conclusion, acute resistance exercise did not result in postexercise suppression of NCMC or LP, and 10 wk of resistance training did not influence resting immune measures in women aged 67-84 yr.     

Proteasome inhibition drastically but reversibly impairs murine lymphocyte development

The proteasome inhibitor bortezomib, which induces cell death in various cancer cell lines including lymphatic neoplasias, has recently been approved for the treatment of relapsed multiple myeloma. Important mechanisms of proteasome inhibitor-mediated tumor cell death are the inhibition of NF-kappaB activation and induction of the terminal unfolded protein response (UPR). However, little is known about effects of bortezomib on developing and mature lymphocytes. Therefore, Balb/C mice were injected with bortezomib and lymphocyte subsets were analyzed. This treatment resulted in dramatically decreased numbers of T and B lymphocyte precursors, while mature lymphocytes were only partially affected. Thymocytes were almost depleted 3 days after a single bortezomib injection, pro-B and pre-B cells already after 2 days. Thymocytes and B cell precursors recovered within 2 weeks. The decreased numbers of developing lymphocytes were due to apoptotic cell death accompanied by strongly increased caspase 3/7 activity. Within 8 h after bortezomib injection, there was a strong induction of heat shock protein 70 and C/EBP homologous protein in bone marrow B cells, indicating endoplasmic reticulum stress and activation of the terminal UPR, respectively. Hence, induction of apoptosis by proteasome inhibition can dramatically affect lymphocyte development, a fact which has important implications for the clinical use of bortezomib, especially in situations with ongoing lymphopoiesis.     

Effect of resistance exercise on dehydroepiandrosterone sulfate concentrations during a 72-h recovery: relation to glucose tolerance and insulin response

Serum dehydroepiandrosterone sulfate (DHEA-S) concentration is known to be associated with the whole-body insulin sensitivity. The main purpose of the study was to investigate the effect of resistance exercise on DHEA-S concentration during a 72 h post-exercise recovery, and its relation to glucose tolerance and insulin sensitivity. Morning fasted serum samples was obtained from 19 male volunteers (aged 21.1+/-0.4 years) 24 h before the onset of exercise and 24 h, 48 h, and 72 h following exercise for measurements of DHEA-S, cortisol, and TNF-alpha. Oral glucose tolerance test (OGTT) and insulin response were determined 24 h before and 48 h after exercise. We found that resistance exercise causes a delayed suppression in serum DHEA-S levels during recovery (48 h and 72 h). This exercise challenge did not affect glucose tolerance, but insulin response during OGTT was significantly elevated. The increased insulin level was not associated with serum levels of cortisol and TNF-alpha. In conclusion, the present study found that resistance exercise has a DHEA-S lowering effect that persisted for 72 h. This change could be related to the elevated insulin concentrations during OGTT.     

Increased lymphocyte antioxidant defences in response to exhaustive exercise do not prevent oxidative damage

It has been reported that exercise induces oxidative stress and causes adaptations in antioxidant defences. The aim of this study was to determine the adaptations of lymphocytes to the oxidative stress induced by an exhaustive exercise. Nine voluntary male subjects participated in the study. The exercise was a cycling mountain stage (171.8 km), and the cyclists took a mean of 283 min to complete it. Blood samples were taken the morning of the cycling stage day, after overnight fasting, and 3 h after finishing the stage. We determined the blood glutathione redox status (GSSG/GSH), lymphocyte antioxidant enzyme activities and superoxide dismutase (SOD) levels; the plasma and lymphocyte vitamin E levels; the serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities and urate levels; the plasma carotene and malonaldehyde (MDA) levels; and the lymphocyte carbonyl index. The cycling stage induced significant increases in blood-oxidized (glutathione/GSSG), plasma MDA and serum urate levels. The exercise also produced increases in CK and LDH serum activities. The mountain cycling stage induced significant increases in lymphocyte vitamin E levels, glutathione peroxidase and glutathione reductase activities as well as increased SOD activity and protein levels. The protein carbonyl levels increased significantly in lymphocytes after the stage. In conclusion, in spite of increasing antioxidant defences in response to the oxidative stress induced by the exhaustive exercise, lymphocyte oxidative damage was produced after the stage as demonstrated by the increased carbonyl index even in very well trained athletes.     

Induction of apoptosis of T cells by infecting mice with murine cytomegalovirus.

Cytomegalovirus (CMV) is associated with several lymphocyte dysfunctions, but the precise mechanisms of the dysfunctions are still unclear. To elucidate the mechanisms, a cell cycle-DNA content analysis was performed on splenic T cells of murine CMV (MCMV)-infected BALB/c mice. T cells from mice infected with 3 x 10(3) PFU of MCMV contained a higher percentage of hypodiploid nuclei after 12 or 24 h of culture than those from naive mice. T cells from infected mice also contained a larger amount of fragmented DNA. Taken together, these results suggested that infection with MCMV induced the apoptotic cell death of T cells. This induction of apoptosis accounted for the dysfunction of lymphocytes, at least partially. Flow cytometric analysis showed that T cells as well as B cells from MCMV-infected mice expressed an augmented level of Fas antigen, an apoptosis-associated cell surface molecule, which might be the cause of the apoptosis of cells. T cells from MCMV-infected C57BL/6-lpr/lpr mice with mutations at the lpr/fas locus, however, also showed a substantial level of apoptosis, which was reproducibly lower than that seen in C57BL/6 mice. Therefore, it was suggested that the Fas-mediated pathway contributed to but was not sufficient for the induction of apoptosis and that mechanisms other than the Fas-associated pathway were also involved in the induction of apoptosis.     

The effect of linoleic acid on the sensitivity of human lymphocytes to cortisol and their capacity to catabolize the steroid

We have shown previously that cortisol-sensitive lymphocytes (thymocytes) have a much lower capacity than cortisol-resistant cells to catabolize cortisol. In the present study, we attempt to demonstrate that inhibition of cortisol catabolism may make cortisol-resistant lymphocytes vulnerable to the steroid. Linoleic acid, which has the capacity to inhibit the catabolism of cortisol by lymphocytes, was used for this purpose. By using various concentrations of linoleic acid (20-60 micrograms/mL) we showed an inverse linear relationship between linoleic acid concentration and the rate of cortisol catabolism by lymphocytes. During this experiment which took 17 h the viability of cells did not change significantly (minimum viability 95%), even at the highest concentration of linoleic acid. Keeping the metabolism of cortisol at a level of 40% of that obtained by the control, by adding linoleic acid to lymphocyte cultures (50 micrograms/mL) and measuring the viability of the cells for a period of 3 days in the presence or absence of cortisol, we were able to show a rise in the death rate of the cells which started after 24 h of incubation owing to the presence of the steroid.     

Studies on the immediate and delayed leucocytosis elicited by brief (30-min) strenuous exercise

Eight healthy male volunteers exercised for two 30-min sessions starting 3 h apart on an electronically braked cycle ergometer at a work load (mean 155.9 W, SD 33.4 W) which required an oxygen consumption that was 70% of their maximal rate of oxygen uptake. Venous blood samples were taken through an indwelling cannula over a period of 6 h beginning shortly before the first bout of exercise and were analysed for routine haematological parameters and for lactate, noradrenaline, adrenaline and cortisol. Both bouts of exercise induced an immediate leucocytosis due to rises in lymphocytes and neutrophils but only the first exercise bout induced a substantial delayed neutrophilia. In at least five subjects, changes in lymphocyte and platelet numbers were correlated (Spearman's rank procedure, P less than 0.05) with simultaneous changes in the plasma concentrations of lactate, noradrenaline and adrenaline over the 6-h period studied. Increases in the plasma concentration of cortisol due to exercise correlated positively with the percentage changes in neutrophil numbers at 3 h and 6 h. These results are consistent with the suggestion that the immediate and delayed leucocytosis induced by exercise are mediated respectively by catecholamine and by cortisol.     

Adrenalectomy in mice does not prevent loss of intestinal lymphocytes after exercise.

Exhaustive exercise is associated with an increase in circulating glucocorticoids (GCs), lymphocyte apoptosis, and a reduction in intestinal lymphocyte number. The present study examined the role of GCs on the numerical changes seen in intestinal lymphocytes after exercise. Female C57BL/6 mice were bilaterally adrenalectomized (ADX; n = 18) or given sham surgery (Sham; n = 18) and assigned to one of three exercise conditions: treadmill running (28 m/min, 90 min, 2 degrees slope) and killed immediately or after 24 h recovery, or not exercised and killed immediately after 90-min exposure to the treadmill environment. Lymphocytes were isolated from the intestines with CD45(+) cells collected by positive selection using magnetic bead separation columns, and lymphocyte subpopulations were analyzed by flow cytometry for CD45(+), CD3alphabeta(+), CD3gammadelta(+), CD8beta(+), CD8alpha(+), CD4(+), and NK(+) phenotypic markers. ADX mice had significantly more intestinal CD45(+) leukocytes (P < 0.05) and CD3alphabeta(+) (P < 0.05), CD3gammadelta(+) (P < 0.01), CD8alpha(+) (P < 0.001), and NK(+) (P < 0.05) intestinal lymphocytes than Sham mice. There was a significant effect of exercise condition on total intestinal CD45(+) leukocytes (P < 0.01) and CD3alphabeta(+) (P < 0.05), CD8alpha(+) (P < 0.001), and CD4(+) (P < 0.05) intestinal lymphocytes, with fewer cells at 24 h postexercise compared with the other treatment conditions. There were no surgical x exercise interaction effects on the CD3 and CD8 phenotype numbers. Plasma corticosterone was virtually nil in ADX mice regardless of exercise condition but was significantly elevated in Sham mice immediately postexercise (P < 0.001). The data indicate that ADX does not prevent the loss of lymphocytes from the intestinal mucosa 24 h after strenuous exercise and GCs are not directly causal in the leukopenia of exercise.     

Hydroquinone-induced apoptosis of human lymphocytes through caspase 9/3 pathway

Hydroquinone (HQ) is a major benzene metabolite, which is produced after benzene biotransformation. In this study, we investigated the toxic effect of HQ on lymphocytes. HQ significantly induced the apoptosis of lymphocytes isolated from normal peripheral blood in both dose and time dependent courses. Volatile organic compounds such as benzene, phenol, formaldehyde, o- and p-xylene, and toluene have no effect on lymphocyte apoptosis. HQ induced the cleavage of procaspase 3 and procaspase 9, indicating activation of the pro-apoptotic enzymes. Supernatant was collected from normal lymphocytes after HQ treatment and it significantly induced the apoptosis of normal lymphocytes as compared to supernatant collected from normal lymphocytes without HQ treatment. HQ reduced the secretion of MCP-1, IL-6 and IL-8 increased by in vitro incubation, although benzene and phenol are not effective in cytokine production. HQ increased the intracellular ROS production of lymphocytes. Benzene and phenol also increased the ROS production. In summary, HQ has a cytotoxic effect on lymphocytes by apoptosis induction and the pro-apoptotic signaling is involved in caspase 9/3 pathway. Our results demonstrated that HQ induces apoptosis by activating caspases 9/3 pathway and that the toxic effect seems to be dependent on lymphocyte metabolism.     

FTY720 reduces post-ischemic brain lymphocyte influx but does not improve outcome in permanent murine cerebral ischemia

Background

The contribution of neuroinflammation and specifically brain lymphocyte invasion is increasingly recognised as a substantial pathophysiological mechanism after stroke. FTY720 is a potent treatment for primary neuroinflammatory diseases by inhibiting lymphocyte circulation and brain immigration. Previous studies using transient focal ischemia models showed a protective effect of FTY720 but did only partially characterize the involved pathways. We tested the neuroprotective properties of FTY720 in permanent and transient cortical ischemia and analyzed the underlying neuroimmunological mechanisms.

Methodology/Principal Findings

FTY720 treatment resulted in substantial reduction of circulating lymphocytes while blood monocyte counts were significantly increased. The number of histologically and flow cytometrically analyzed brain invading T- and B lymphocytes was significantly reduced in FTY720 treated mice. However, despite testing a variety of treatment protocols, infarct volume and behavioural dysfunction were not reduced 7d after permanent occlusion of the distal middle cerebral artery (MCAO). Additionally, we did not measure a significant reduction in infarct volume at 24h after 60 min filament-induced MCAO, and did not see differences in brain edema between PBS and FTY720 treatment. Analysis of brain cytokine expression revealed complex effects of FTY720 on postischemic neuroinflammation comprising a substantial reduction of delayed proinflammatory cytokine expression at 3d but an early increase of IL-1β and IFN-γ at 24 h after MCAO. Also, serum cytokine levels of IL-6 and TNF-α were increased in FTY720 treated animals compared to controls.

Conclusions/Significance

In the present study we were able to detect a reduction of lymphocyte brain invasion by FTY720 but could not achieve a significant reduction of infarct volumes and behavioural dysfunction. This lack of neuroprotection despite effective lymphopenia might be attributed to a divergent impact of FTY720 on cytokine expression and possible activation of innate immune cells after brain ischemia.     

Human lymphocyte apoptosis after exposure to influenza A virus

Infection of humans with influenza A virus (IAV) results in a severe transient leukopenia. The goal of these studies was to analyze possible mechanisms behind this IAV-induced leukopenia with emphasis on the potential induction of apoptosis of lymphocytes by the virus. Analysis of lymphocyte subpopulations after exposure to IAV showed that a portion of CD3(+), CD4(+), CD8(+), and CD19(+) lymphocytes became apoptotic (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling positive). The percentage of cells that are infected was shown to be less than the percentage of apoptotic cells, suggesting that direct effects of cell infection by the virus cannot account fully for the high level of cell death. Removal of monocytes-macrophages after IAV exposure reduced the percent of lymphocytes that were apoptotic. Treatment of virus-exposed cultures with anti-tumor necrosis factor alpha did not reduce the percentage of lymphocytes that were apoptotic. In virus-exposed cultures treated with anti-FasL antibody, recombinant soluble human Fas, Ac-DEVD-CHO (caspase-3 inhibitor), or Z-VAD-FMK (general caspase inhibitor), apoptosis and production of the active form of caspase-3 was reduced. The apoptotic cells were Fas-high-density cells while the nonapoptotic cells expressed a low density of Fas. The present studies showed that Fas-FasL signaling plays a major role in the induction of apoptosis in lymphocytes after exposure to IAV. Since the host response to influenza virus commonly results in recovery from the infection, with residual disease uncommon, lymphocyte apoptosis likely represents a part of an overall beneficial immune response but could be a possible mechanism of disease pathogenesis.     

Kinetics of 21-trisomic lymphocytes

Summary Data presented here on the quantitative ³H-thymidine incorporation into DNA, after PHA mitogenic stimulation, show that 21-trisomic lymphocytes are low-responders to PHA compared with the normal-diploid ones. Their responsiveness seems to decrease with the donor's age. Autoradiographic studies clearly demonstrate that the fraction of labeled cells at the 72nd h of incubation is significantly smaller in the 21-trisomic lmphocyte population. The comparison of labeling indexes at different times of incubation (24, 48, 72 h) also indicate, in the same population, a slower increment of the portion of DNA-synthesizing cells. Discussing these data in the light of other's observations and recent progress in the knowledge of factors and mechanisms involved in the lymphocyte response to lectin mitogenic stimulus, it is suggested that differential distribution of T- and B- and/or T-cell sub-populations and a retarded cell induction time to proliferate may be two important factors negatively influencing the responsiveness of 21-trisomic lymphocyte population.     

High Intensity Exercise: A Cause of Lymphocyte Apoptosis?

Post exercise lymphocytopenia is well documented and attributed to egress of lymphocytes from the vascular compartment. Recent studies have reported exercise induced DNA damage in leukocytes and have questioned a possible link to apoptosis. Eleven subjects underwent a ramped treadmill test to exhaustion. Venous blood samples were taken before, immediately post exercise, and 24 and 48 hours after exercise. Single cell gel electrophoresis revealed evidence of single strand DNA damage in 10% of lymphocytes immediately after exercise, but not at other times. Fluorescent microscopy showed three patterns of DNA distribution, similar to those seen in apoptosis, at all times after exercise. Three subjects underwent the same exercise protocol, and lymphocytes were prepared for flow cytometry to determine apoptosis using the TUNEL method. Flow cytometry revealed lymphocyte apoptosis in 63% of lymphocytes immediately after exercise and 86.2%, 24 hours after exercise. Lymphocyte apoptosis is documented for the first time after exercise and may in part account for exercise induced lymphocytopenia and reduced immunity.     

N-Acetyl-L-cysteine prevents exercise-induced intestinal lymphocyte apoptosis by maintaining intracellular glutathione levels and reducing mitochondrial membrane depolarization

Intense exercise leads to post-exercise lymphocytopenia and immunosuppression, possibly by triggering lymphocyte apoptosis. To test the role of oxidative stress on exercise-induced lymphocyte apoptosis, we administered the antioxidant N-acetyl--cysteine (NAC) and measured apoptosis in intestinal lymphocytes (IL) from exhaustively exercised animals. Eighty-seven female C57BL/6 mice were randomly assigned to receive NAC (1 g/kg) or saline 30 min prior to treadmill exercise for 90 min at 2degrees slope (30 min at 22 m min(-1), 30 min at 25 m min(-1), and 30 min at 28 m min(-1)) and sacrificed immediately (Imm) or 24 hours (24 h) after cessation of exercise. Control mice (nonexercised) were exposed to treadmill noise and vibration without running. Exercise increased IL phosphatidylserine externalization (p<0.001), mitochondrial membrane depolarization (p<0.05), and decreased intracellular glutathione concentrations (p<0.05) immediately following exercise in saline relative to nonexercised mice. At 24 h post-exercise, saline injected mice had fewer total (p<0.001) and CD3+ (p<0.005) IL compared to nonexercised animals. NAC injection in mice maintained intracellular glutathione levels, prevented phosphatidylserine externalization, mitochondrial membrane depolarization, and loss of IL immediately and 24 h after exercise. These data suggest that lymphocyte apoptosis precedes post-exercise lymphocytopenia and may be due to oxidative stress.     

White blood cell response to uphill walking and downhill jogging at similar metabolic loads

The object of this study was to determine whether leukocytosis would occur in response to eccentric exercise, to concentric exercise, and/or to possible increases in serum cortisol levels. Eight men performed 2 bouts of exercise at 46% VO2max for 40 min. Subjects initially walked up a 10% grade (UW); 2 weeks later they jogged down a 10% grade (DJ), a form of eccentric exercise known to induce delayed onset muscle soreness (DOMS). Venous blood samples were drawn before and after each exercise bout (0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, and 5 h). Total and differential WBCc and serum cortisol levels were assessed. Results were analyzed using repeated measures ANOVA (2 x 11). Subjects experienced severe DOMS after DJ. There was a significant difference in TWBCc (p less than 0.0001) between UW and DJ. Post-hoc testing revealed no significant increase over baseline values for UW; after DJ there was a 46% increase over baseline values (p less than 0.05) initially seen at 1.0 h. These increases in TWBCc were predominantly a reflection of increases in neutrophils which were significant (p less than 0.0001) when compared to baseline values at 1.0, 1.5 and 2.0 h (approximately 60%). No significant neutrophil increases were seen after UW. Cortisol levels were similar for both groups pre-exercise (UW = 367.1 +/- 38.6, DJ = 320.2 +/- 44.16 nmol.L-1 means +/- SE) and decreased similarly for both groups after exercise, and thus were not related to the post-exercise neutrophilia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of antiglobulin serum on the expression of M-cholinoreceptors of spleen lymphocytes of intact and immunized mice

Using a labelled blocker of M-cholinoreceptors (M-CR)--3H-Quinuclidinyl benzilate--the number of the receptors on spleen lymphocytes has been determined before and after immunization of CBA and BALB/c mice with antiglobulin serum. The incubation of non-separated spleen cell suspension with antiglobulin serum decreased the number of M-CR by 14%, while the incubation of the enriched B-lymphocyte suspension decreased it by 32.5%. The immunization of animals with ovalbumin or bovine red blood cells increased the serum effect on M-CR expression in non-separated lymphocyte suspension and had practically no influence on the serum effect in B-lymphocyte suspension. Thus, the effect on immunoglobulin receptors of B lymphocytes has a pronounced influence on M-CR expression, which may be one of the mechanisms of nervous and immune systems interaction.     

Cell numbers and in vitro responses of leucocytes and lymphocyte subpopulations following maximal exercise and interval training sessions of different intensities.

In vitro lymphocyte function and the mobilisation of peripheral blood leucocytes was examined in eight trained subjects who undertook an incremental exercise test to exhaustion and a series of interval training sessions. Venous blood samples were obtained before the incremental test, immediately after, and 30, 60, and 120 min after the test. Interval training sessions were undertaken on separate days and the exercise intensities for each of the different sessions were 30%, 60%, 90% and 120% of their maximal work capacity respectively, as determined from the incremental exercise test. There were 15 exercise periods of 1-min duration separated by recovery intervals of 2 min in each session. Venous blood samples were obtained immediately after each training session. Significant increases in lymphocyte subpopulations (CD3+, CD4+, CD8+, CD20+, and CD56+) occurred following both maximal and supramaximal exercise. This was accompanied by a significant decrease in the response of cultures of peripheral blood lymphocytes to Concanavalin A (ConA), a T-cell mitogen. The state of lymphocyte activation in vivo as measured by CD25+ surface antigen was not, however, affected by acute exercise. The total number of lymphocytes, distribution of lymphocyte subpopulations and in vitro lymphocyte response to ConA had returned to pre-exercise levels within half an hour of termination of exercise but serum cortisol concentrations had not begun to fall at this time. There was a significant decrease in the CD4+:CD8+ cell ratio following exercise; this was more the result of increases in CD3-CD8+ cells (CD8+ natural killer cells) than to CD3+CD8+ cells (CD8+ T-lymphocytes). Decreased responsiveness of T-cells to T-cell mitogens, postexercise, may have been the result of decreases in the percentage of T-cells in postexercise mixed lymphocyte cultures rather than depressed cell function. The cause of this was an increase in the percentage of natural killer cells which did not respond to the T-cell mitogen. The results indicated that while a substantial immediate in vitro "immunomodulation" occurred with acute exercise, this did not reflect an immunosuppression but was rather the result of changes in the proportions of reactive cells in mononuclear cell cultures. We have also demonstrated that the degree of the change in distribution of lymphocyte subpopulation numbers and responsiveness of peripheral blood mononuclear cells in in vitro mitogen reactions increased with increasing exercise intensity. Plasma volume changes may have contributed to some of the changes seen in leucocyte population and subpopulation numbers during and following exercise.     

Change in acid phosphatase and N-acetyl-beta-glucosaminidase activity in mouse lymphocytes induced by concanavalin A

The treatment with concanavalin A (5 micrograms/ml) of mouse lymphocytes containing 70-72% of T cells entails an increase in the activity of acid phosphatase and a decrease in the activity of N-acetyl-beta-glucosaminidase. These changes were detectable 15 h after lymphocyte incubation with Con A. After 24 h of incubation acid phosphatase activity rose 2-fold whereas that of N-acetyl-beta-glucosaminidase dropped 45-50%. Possible mechanisms of these changes are discussed.     

Modulation of programmed death of the peripheral blood lymphocytes under chronic virus infection

We investigated programmed death of lymphocytes in patients with chronic infections--tick-borne encephalitis, hepatitis B and C. It has been shown that the character of disorders in realization of lymphocyte apoptosis depends on molecular features of the infectious agent. Apoptotic death of lymphocytes was elevated after incubation in vitro with dexamethazone, etopozide and in medium without serum. Receptor-dependent and mitochondrial paths of apoptotic signal conduction are preferentially modulated under chronic virus persistence.