Neonatal capsaicin treatment affects rat thymocyte proliferation and cell death by modulating substance P and neurokinin-1 receptor expression

Herein we provide evidence that substance P (SP) and its neurokinin-1 receptor (NK-1R) expressed on thymocytes counteract thymus depletion induced by neonatal capsaicin (CPS) treatment by affecting thymocyte proliferation and apoptotic death. SP administration reversed the CPS-mediated inhibitory effects on the total thymocyte number and subset distribution, namely CD4+ and CD4- CD8- cells, through its interaction with NK-1R as shown by concomitant NK-1R (SR140333) antagonist administration. SP-induced enhancement of thymus cellularity parallels its ability of inhibiting the thymocyte apoptotic program. Indeed, exogenously administered SP completely nullified CPS-induced apoptosis, and SR140333 abrogated the SP-mediated protective effect. SP administration also stimulated concanavalin A (Con A)-induced thymocyte proliferation of CPS-treated rats, completely reversing the CPS-induced inhibition. The SP-mediated stimulation of Con A-induced thymocyte proliferation was NK-1R dependent as shown by concomitant administration of SP and SR140333 to CPS-treated rats. Our results also demonstrate that CPS treatment induces a marked decrease of thymocyte PPT-A mRNA level and endogenous SP content as evaluated by quantitative RT-PCR, in situ hybridization and cytofluorimetric analysis. By contrast, NK-1R mRNA levels were increased in thymocytes from CPS-treated rats. Exogenous SP administration augmented PPT-A, SP and NK-1R thymocyte expression in CPS-treated rats, and this enhancement was antagonized by SR140333 administration. Overall, our results strongly suggest that the immunomodulatory effects of neonatal CPS treatment on rat thymocyte functions are dependent on vanilloid-mediated regulation of SP and NK-1R functional expression by neuronal and immune cells.     

Expression of substance P and its neurokinin-1 receptor on thymocytes: functional relevance in the regulation of thymocyte apoptosis and proliferation

Herein, we provide evidence of the expression and function of substance P (SP) and neurokinin-1 receptor (NK-1R) in the rat thymus. In situ hybridization evidenced NK-1R mRNA mainly in the thymic medulla, and Northern blot analysis of mRNA from FACS-sorted thymocytes identified NK-1R on CD4+, CD8+ and double-positive subpopulations. With flow cytometry, it could be seen that NK-1R was expressed on the majority of CD5+ thymocytes, and it was identified by Western blot analysis as two bands migrating at 44 and 54 kD. SP administration rescues thymocytes from spontaneous and NK-1R antagonist (SR140333)-induced apoptosis and stimulates concanavalin A (ConA)-induced thymocyte proliferation, CD25 expression and IL-2 production, whereas SR140333 exerts inhibitory effects on these functions. We also demonstrated the expression of mRNA for the SP precursor preprotachykinin-A in the thymic medulla and purified CD5+ thymocytes. SP protein was detected on 40% of CD5+ thymocytes and identified as a band of 1.3 kD by Western blot analysis. Finally, thymocytes spontaneously released SP, which was increased upon ConA or CD3 stimulation.     

Differential effects of light/dark recombinant human prolactin administration on the submaxillary lymph nodes and spleen activity of adult male mice

OBJECTIVES: Day/night variations in cellularity, percentage of CD4+, CD8+ and double-positive (CD4+-CD8+) lymphocytes, lipopolysaccharide (LPS)- and concanavalin A (Con A)-induced lymphocyte proliferation and natural killer (NK) activity, and the effect of timed administration of recombinant human prolactin (h-PRL) on the above-mentioned parameters were investigated in the submaxillary lymph nodes and spleen of adult male mice. RESULTS: In controls, the percentage of CD4+, double-positive lymphocytes, LPS- or Con A-induced blastogenic proliferation and NK activity in the spleen differ during the dark phase as compared to the light phase. When administered during the dark period, h-PRL induced immunosuppresion in the percentage of CD4+, double-positive (CD4+-CD8+) lymphocytes. Con A- and LPS-induced lymphocyte proliferation and NK activity as compared to untreated controls. When h-PRL was administered during the light period, the cellularity increased, and h-PRL was immunosuppressive in Con A- and LPS-induced lymphcoyte proliferation and NK activity as compared to controls. Moreover, in control submaxillary lymph nodes the cellularity, percentage of CD8+, double-positive lymphocytes, blastogenic proliferation in the presence of Con A and LPS and NK activity differ when comparing the dark with the light phase. When administered during the dark period h-PRL induced immunosuppression in the percentage of double-positive (CD4+-CD8+) lymphocytes, Con A- and LPS-induced lymphocyte proliferation as compared to controls. When h-PRL is administered during the light period, no effects were observed. CONCLUSIONS: These results indicate the existence of differential day/night variations in the cellular immune response depending upon the lymphoid organ considered. Because of the administration of h-PRL a differential modulation of this circadian variation was also observed.     

Alterations in T lymphocyte activity following chemical sympathectomy in young and old Fischer 344 rats

In aged Fischer 344 (F344) rats, sympathetic noradrenergic (NA) innervation of the spleen is markedly diminished compared with young rats. To determine if diminished NA innervation can still provide functional signals to splenic T cells, young (3 months old) and old (17 months old) F344 rats were treated with the NA-selective neurotoxin, 6-hydroxydopamine (6-OHDA) to destroy peripheral NA nerve fibers. In 3-month-old rats, no alterations in spleen cell Con A-induced T cell proliferation, IL-2 or IFN-gamma production were observed up to 15 days after sympathectomy, when splenic NE was maximally depleted. By 21 days post-sympathectomy, when NE levels had partially recovered, Con A-induced proliferation and IFN-gamma production, but not IL-2 production, were reduced in sympathectomized animals. After day 21 post-sympathectomy, no alterations in T cell functions were observed in sympathectomized animals. In 17-month-old rats, spleen cell Con A-induced proliferation and IL-2 production were reduced 5 days after sympathectomy in the absence of changes in CD5+ T cells or IFN-gamma production. Desipramine pretreatment, to block 6-OHDA uptake and prevent sympathectomy, completely blocked the 6-OHDA-induced effects, demonstrating that the destruction of NA nerve fibers is required. After day 5 post-sympathectomy, no sympathectomy-induced alterations in Con A-induced T cell functions were observed in old animals. These differences between young and old rats demonstrate that old animals are more susceptible to loss of sympathetic NA innervation, perhaps because compensatory mechanisms are limited. The sympathectomy-induced reduction in T cell proliferation indicates that splenic NA innervation in old animals, though diminished, can exert a positive regulatory influence on T lymphocyte function. Further study of sympathetic neural-immune interactions in the aged rat may provide a means to improve T cell responsiveness in aging.     

Interleukin-18 mRNA expression in the rat pituitary gland

Substance P (SP) is a modulatory, pro-inflammatory neuropeptide. We investigated the role of the SP receptor, neurokinin-1 (NK-1), in EAE. Our data show that in the chronic phase, mice lacking NK-1 have improved mobility and decreased numbers of LFA-1 high CD4+ T cells and MOG-specific, IFN-γ producing CD4+ T cells. SR140333, an NK-1 antagonist, administered alone during the chronic phase of EAE was not sufficient to ameliorate symptoms. These results indicate that SP, through NK-1, contributes to maintenance of CNS inflammation, and combining NK-1 antagonists with conventional anti-inflammatory treatments may enhance the success of treatments for diseases like multiple sclerosis.     

B7 expression and antigen presentation by human brain endothelial cells: requirement for proinflammatory cytokines

Interaction between systemic immune cells with cells of the blood-brain barrier is a central step in development of CNS-directed immune responses. Endothelial cells are the first cells of the blood-brain barrier encountered by migrating lymphocytes. To investigate the antigen-presenting capacity of human adult brain endothelial cells (HBECs), we used HBECs derived from surgically resected temporal lobe tissue, cocultured with allogeneic peripheral blood derived CD4+ T lymphocytes. HBECs in response to IFN-gamma, but not under basal culture conditions, expressed HLA-DR, B7.1 and B7.2 antigens. Despite such up-regulation, these IFN-gamma-treated HBECs, in contrast to human microglia and PB monocytes, did not sustain allogeneic CD4+ cell proliferation, supported only low levels of IL-2 and IFN-gamma production, and did not stimulate IL-2 receptor expression. CD4+ T cell proliferation and increased IL-2 receptor expression could be obtained by addition of IL-2. Our data suggests that, although HBECs cannot alone support T cell proliferation and cytokine production, HBECs acting in concert with cytokines derived from a proinflammatory environment could support such a response.     

Effects of L-deprenyl treatment on noradrenergic innervation and immune reactivity in lymphoid organs of young F344 rats

Sympathetic noradrenergic (NA) neuronal activities in the thymus, spleen and mesenteric lymph nodes (MLN) and immune responses in the spleen were examined in young male F344 rats treated daily with 0, 0.25 mg, or 2.5 mg/kg body weight of L-deprenyl, an irreversible monoamine oxidase-B (MAO-B) inhibitor. Rats were treated daily for 1, 15, or 30 days, and sacrificed 7 days after the last deprenyl treatment. Deprenyl treatment increased norepinephrine (NE) content in the spleen without modifying the pattern and density of NA innervation in the splenic white pulp. The concentration of NE was unaltered in the thymus, but it was increased in the MLN of deprenyl-treated rats. One day of treatment with deprenyl decreased splenic NK cell activity while 15 days of deprenyl treatment enhanced splenic NK cell activity. Deprenyl elevated Con A-induced T lymphocyte proliferation following 30 days of treatment, but did not alter spleen cell Con A-induced IL-2 production or the percentage of CD5 + T cells in the spleen. A moderate decrease in the percentage of sIgM + B cells was observed in the spleens of 15- and 30-day deprenyl-treated rats. These results suggest that deprenyl has sympathomimetic action on sympathetic NA nerve fibers in the spleen; the enhancement of NA neuronal activity may contribute to the modulation of immune responses in the spleen.     

A study of associated cell-mediated immune mechanisms in experimental autoimmune neuritis rats

The aims of this study are to investigate the optimal antigens used to induce acute or chronic EAN and the associated cell-mediated immune mechanisms. Lewis rats were grouped into EAN rats and control rats. EAN rats were immunized by injection into both hind footpads of inoculums containing 100 microg/200 microg of P2 peptide 57-81 and FCA, or 200 mug of P0 peptide 180-199 and FCA. Control rats were immunized by FCA. Clinical scores were compared at the maximum of disease. On the 14th day after immunization, we examined lymphocyte proliferation, fractions of CD4+ T cells within lymph node mononuclear cells (MNC), frequencies of CD4+CD25+ T cells within CD4+ T cells, supernatant productions of IFN-gamma, IL-4, IL-10 and TGF-beta1 secreted by lymphocytes. Histopathology of sciatic nerves was assessed. Our findings indicated: (1) 100 microg of P2 peptide 57-81 and 200 microg of P0 peptide 180-199 may induce an acute EAN and 200 microg of P2 peptide 57-81 may induce a chronic EAN; (2) Lewis rats were more sensitive to P2 peptide 57-81 than P0 peptide 180-199; (3) clinical disease had nothing to do with a change of relative CD4+ T cells number in lymph node MNC; (4) frequencies of CD4+CD25+ T cells and levels of TGF-beta1 secreted by lymphocytes negatively paralleled clinical EAN, while levels of IFN-gamma secreted by lymphocytes roughly paralleled clinical EAN at the acute phase; (5) sciatic nerve sections from the chronic EAN rats didn't show any inflammatory cells, but showed remaining segmental demyelination and axonal collapse at the chronic phase; (6) self-limitation of acute EAN may owe to the rising levels of IL-4 and IL-10, while a longer duration of chronic EAN may owe to the decreasing levels of IL-4 and IL-10.     

Immunotherapy of rat glioma without accumulation of CD4~+CD25~+FOXP3~+ regulatory T cells

Immunotherapy may be used for the treatment of glioblastoma multiforme;however,the induced immune response is inadequate when either T cells or dendritic cells are used alone.In this study,we established a novel vaccine procedure in rats,using dendritic cells pulsed with C6 tumor cell lysates in combination with adoptive transfer of T lymphocytes from syngenic donors.On day 21 after tumor inoculation,all the rats were sacrificed,the brains were harvested for calculation of glioma volume,cytolytic T lymphocyte responses were measured by cytotoxic assay,and the frequency of regulatory T lymphocytes(CD4+CD25+FOXP3+) in the peripheral blood was investigated by flow cytometric analysis.The survival rate of rats bearing C6 glioma was observed.Results showed that the co-immunization strategy had significant anti-tumor potential against the pre-established C6 glioma,and induced a strong cytolytic T lymphocyte response in rats.The frequency of peripheral blood CD4+CD25+FOXP3+ regulatory T lymphocytes was significantly decreased following the combination therapy,and the rats survived for a longer period.Experimental findings indicate that the combined immunotherapy of glioma cell lysate-pulsed dendritic cell vaccination following adoptive transfer of T cells can effectively inhibit the growth of gliomas in rats,boost anti-tumor immunity and produce a sustained immune response while avoiding the accumulation of CD4+CD25+FOXP3+ regulatory T lymphocytes.     

Preferential increase of IL-2R+ CD4+ T cells and CD45RB- CD4+ T cells in the central nervous system in experimental allergic encephalomyelitis.

We examined lymphocytes isolated from the spinal cord (SC), peripheral blood (PB) and lymph nodes (LN) draining the immunization site of Lewis rats with acute experimental allergic encephalomyelitis (EAE). Cells were analysed for T cell subset markers CD4 (mAb W3/25) and CD8 (mAb OX8), for IL-2R (mAb OX39), and for high molecular mass leukocyte common antigen (LCA, CD45RB) expression (mAb OX22). T cells expressing high (CD45RB+) or low (CD45RB-) molecular mass LCA are of different maturational stages and/or separate lineages. CD4+ T cells were more predominant in SC than in PB and LN; CD8+ T cells were scarce in SC but common in PB and LN. Activated CD4+ T cells (IL-2R+) were common in the SC and LN but infrequent in blood. CD4+ T cells that were CD45RB+ were scarce in the SC. In contrast, the majority of CD4+ T cells in the PB and LN were CD45RB+. The preferential accumulation of IL-2R+ CD4+ T cells and of CD45RB- CD4+ T cells in the central nervous system (CNS) indicates that a selective mechanism directs cell egress into CNS lesions in EAE.     

脑胶质瘤热休克蛋白抗原肽复合物抑瘤作用的研究

目的提纯大鼠脑胶质瘤C6细胞热休克蛋白抗原肽复合物(HAC),免疫大鼠,观察HAC的抑瘤作用。方法采用免疫亲和层析方法提纯鼠脑胶质瘤C6细胞HAC,免疫20只大鼠为实验组,以另20只大鼠作为对照组,于免疫后一周,采用立体定向脑内接种方法,以C6细胞攻击两组大鼠,于肿瘤细胞攻击后第二周,进行外周静脉血淋巴细胞计数,和血清INF、IL-2、TNF的浓度测定,并于正常对照。观察四周后动物的存活率。进行HE染色,并用免疫组化方法分析脑胶质瘤浸润区T淋巴细胞分布情况。结果实验组大鼠外周血淋巴细胞计数和IFN、IL-2、TNF浓度均显著高于对照组(P<0.01)。实验组胶质瘤局部浸润的CD3+和CD4+细胞数均显著高于对照组(P<0.01),CD8+细胞数与对照组比较无显著差异(P>0.05),T淋巴细胞CD4+/CD8+显著高于对照组(P<0.01)。结论C6细胞中HAC可以诱导大鼠产生对C6细胞的细胞免疫,抑制肿瘤生长,提高接种大鼠存活率。     

Thymic output and peripheral T lymphocyte subsets in relapsing--remitting multiple sclerosis patients treated or not by IFN-beta

We explored the parameters of central and peripheral tolerance in patients with stable relapsing-remitting multiple sclerosis, treated or not with IFN-beta. TREC-positive T cells were lower in patients compared with controls, mainly in CD4+ subset, compatible with a thymus dysfunction or an expansion of peripheral lymphocytes. Compared to controls, the frequency of activated CD4+CD25+ T cells was higher in patients without modification of the CD4+CD25(high) T cell proportion. The IFN-beta-treatment did not modify the TREC-positive cell frequency nor the naive/memory T cell subset percentage but was associated with lower blood lymphocyte count and a lower frequency of CD4+CD45RC(high) subset.     

Intracellular cytokine profile in T-cell subsets of multiple sclerosis patients: different features in primary progressive disease

OBJECTIVE: To evaluate the expression of cytokines in both CD4+ and CD8+ T cells derived from peripheral blood of untreated multiple sclerosis (MS) patients with either relapsing-remitting (RR), secondary progressive (SP) or primary progressive (PP) MS and healthy controls (HC). BACKGROUND: MS is an immune-mediated disease and cytokines hove been hypothesized to contribute significantly to disease progression. Compared to the relapse-onset (RR, SP) form of the disease, PPMS patients have different clinical, immunological and pathological features. Surprisingly, the ability of their circulating T cells to produce immunoregulatory cytokines has not been extensively studied so far. METHODS: Seventy-two MS patients (24 RR, 26 SP, 22 PP) and 34 HC were studied. Stimulated peripheral blood derived CD4+ and CD8+ T MS patients express significantly more CD4+ and CD8+ T cells were analyzed for IFN-gamma, IL-2, TNF-alpha, IL-4, IL-10 and IL-13 production. RESULTS: cells producing IFN-gamma compared to HC. Compared to the other forms of the disease, PPMS patients display a significant decrease in CD4+ T cells producing IL-2, IL-13 and TNF-alpha and a significant increase in CD8+ T cells producing IL-4 and IL-10. CONCLUSIONS: The data presented here demonstrate that patients with PPMS express less pro- and more anti-inflammatory cytokine producing T cells compared to the relapse-onset form of the disease, confirming the view on PPMS as a distinct disease entity.     

Increased sialyl Lewis(x) antigen-positive cells mediated by HTLV-1 infection in peripheral blood CD4(+) T lymphocytes in patients with HTLV-1-associated myelopathy

Sialyl Lewis(x) antigen-positive (sLe(x+)) cells play an important role in the first step of transmigration of T lymphocytes through vascular endothelial cells into tissues. We compared the proportion of sLe(x+) cells in peripheral blood CD4(+) T lymphocytes between patients with HTLV-1-associated myelopathy (HAM) and control patients, by using flow cytometry. The percentage of sLe(x+) cells in peripheral blood CD4(+) T lymphocytes was significantly higher in HAM patients compared to control patients. Interferon-gamma (IFN-gamma), but not interleukin-4 (IL-4), production by the sLe(x+) cell population of peripheral blood CD4(+) T lymphocytes was significantly higher in HAM patients than in control patients. In addition, comparison of the HTLV-1 proviral load between sLe(x+) and sLe(x-) cells in peripheral blood CD4(+) T lymphocytes of HAM patients showed that the HTLV-1 proviral load was significantly higher (two- to eight-fold), concomitant with enhanced IFN-gamma production, in the sLe(x+) than in the sLe(x-) cell population. Our findings indicate that the sLe(x+) cell population, which has features of activated Th1 cells with up-regulated expression of E- and P-selectin ligands mediated by HTLV-1 infection, is increased in peripheral blood CD4(+) T lymphocytes in HAM patients, suggesting their involvement in transmigration of peripheral T lymphocytes from the peripheral blood into tissues.     

Pharmacological hyperprolactinemia attenuates hydrocortisone-induced expression of CD11b on human CD8+ cells in vivo

OBJECTIVE: To study the short-term influences of pharmacologic hyperprolactinemia on hydrocortisone (HC)-induced effects on selected immune parameters. METHODS: A single dose of HC (40 mg per os) was administered to eleven healthy female volunteers 1 h after domperidone (10 mg per os) or placebo administration. Immune cell subsets and expression of adhesion molecules was assessed by flow cytometry at baseline and 4 and 6 h after HC administration. Intracellular staining of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) production in CD4+ lymphocytes after phorbol myristate acetate and ionomycin stimulation was performed at the same time points. RESULTS: HC administration was followed by a significant increase in cortisol levels, numbers of leukocytes and granulocytes and the percentage of CD16+, CD19+, CD11a+, CD11a+CD8+, CD11b+ and CD11b+CD8+ cells. The number of lymphocytes and monocytes and the percentage of CD3+, CD4+, CD4+/CD8+ ratio, CD62L+, CD54+ and CD54+CD16+ cells decreased, while the percentage of CD8+ cells was unaffected. Domperidone administration resulted in a significant increase in prolactin (PRL) concentrations. During hyperprolactinemia, the HC-induced increase in CD11b+CD8+ cells was significantly (p < 0.05) attenuated at 4 h. HC-induced changes in other immune parameters remained unaffected. No significant changes in the intracellular production of IL-4 and IFN-gamma in CD4+ lymphocytes were observed after a single dose of HC alone or during hyperprolactinemia. CONCLUSIONS: This study shows an attenuated HC-induced increase in CD11b+CD8+ cells in the peripheral blood of healthy females during hyperprolactinemia. Our in vivo observations suggest that short-term interactions occur between PRL and glucocorticoids, affecting selected immune functions. Further studies are needed for confirmation of these results.     

In vivo effects of beta-endorphin on lymphocyte proliferation and interleukin 2 production

Experiments were undertaken in rats to investigate the effects of in vivo infusion of beta-endorphin (BEP) on subsequent Con A-induced proliferation and interleukin 2 (IL-2) production by spleen cells in vitro. BEP administration induced a dose-dependent enhancement of the proliferative response to Con A. Infusion of the opiate antagonist naloxone (NAL) inhibited the Con A response and infusion of NAL prior to BEP resulted in even further inhibition. None of these treatments resulted in detectable alterations in IL-2 production after 48 h in culture. To demonstrate a direct interaction between BEP and lymphocytes, spleen cells were incubated in vitro with varying concentrations of BEP and/or NAL. Enhanced Con A-induced proliferation was observed following incubation with BEP in the range 10(-12) to 10(-9) M (levels comparable to the effective in vivo doses) and this effect was abrogated by NAL pretreatment (10(-6) M). These data indicate a role for BEP in enhancing lymphocyte reactivity which is to some extent dependent on opiate receptors on the cell surface. This report extends the evidence obtained from in vitro experiments implicating endogenous opioids in modulation of host immunity by demonstrating that these effects can be obtained in vivo.     

Flow cytometric analysis of lymphocytes in cerebrospinal fluid in patients with tick-borne encephalitis

Introduction – Cerebrospinal fluid (CSF) lymphocyte subsets were examined by flow cytometry in 33 patients with tick-borne encephalitis (TBE) in order to determine their values. Patients and methods – Lymphocytes were isolated from CSF and lymphocyte subsets were determined: lymphocytes T (CD3+), lymphocytes B (CD19+), NK cells (CD3-CD56+), helper T cells (CD3+CD4+) and cytotoxic T cells (CD3+CD8+). The expression of IL-2 receptors (CD25+) and transferrin receptors (CD71+) on T cells and HLA-DR molecules on T cell subsets was examined. Furthermore, possible relationships among different TBE patient population variables (gender, age, severity of disease, duration of meningitis) were considered. Results – The analyses of the CSF lymphocyte population subsets are presented. Lymphocytes T (CD3+) were significantly higher in the CSF than in the peripheral blood as was the case with the T cells that expressed transferrin receptors (CD71). Lymphocytes B (CD19+) and NK cells (CD3-CD56+) prevailed in the peripheral blood. In the early course of the disease, a higher expression of HLA-DR molecules on T lymphocytes was observed, while later a higher expression of IL-2 receptors (CD25+) was observed. Discussion – Significant differences in lymphocyte subsets between the CSF and the peripheral blood were found. Significant time-dependent changes of CSF lymphocyte subsets during course of infection were observed. The results of the present study give us deeper insight into CNS cellular immunopathogenic mechanisms in patients with TBE.     

CD21 (B2 antigen) cell decrement and CD4 CD29 (helper-inducer) cell increment suggest an activation of cell immune reactivity in multiple sclerosis

Two-color flow cytometric analysis on peripheral blood lymphocytes of 35 untreated multiple sclerosis (MS) patients, 17 other medical disease (OMD) patients and 14 healthy control (HC) subjects was performed to evaluate the levels of different T and B cell subpopulations. In MS patients we observed an increase in CD4+CD29+ helper-inducer cells but this increase was not related to the different phases of the disease. We hypothesize that this change is related to the reduction of CD21+ cells expressing B2 antigen, a 140 kDa molecule disappearing after B cell activation. An increased level of CD4+CD45RA- (helper-inducer-like cells) and a reduction of CD4+CD29- (suppressor-inducer-like cells) were also present in our patients. These findings demonstrate an immune 'disequilibrium' in MS, which is linked with an increased level of CD25+ cells expressing the interleukin-2 (IL-2) receptor. IL-2, besides being a T cell growth factor, is also a B cell growth factor. These data let us hypothesize that an activation of the immune response is present in MS.     

CD95/Fas expression on peripheral blood T lymphocytes in patients with multiple sclerosis: effect of high-dose methylprednisolone therapy

Recent data indicate that the apoptotic process, mediated by the CD95/Fas cell surface receptor, is impaired in activated lymphocytes of patients with relapsing-remitting multiple sclerosis. Using flow cytometric-immunophenotyping, we analyzed the expression of CD95/Fas on peripheral blood CD4+ and CD8+ T lymphocytes (PBL) in 10 MS patients in relapse, and the effect of pulse corticosteroid therapy on the apoptosis of autoreactive lymphocytes. The proportions of CD8+ and CD8+CD95+ T lymphocytes were significantly higher in MS patients in relapse before than after pulse corticosteroid therapy. Conversely, the proportions of CD4+ and CD4+CD95+ T cells were significantly lower before than after therapy, but not significantly different from healthy persons. The different expression of CD95/Fas on peripheral blood CD8+ T lymphocytes in relapsing RRMS and in healthy controls suggests a possible involvement of apoptosis in the pathogenesis of MS. Our results also show that pulse corticosteroid therapy influences the CD95/Fas expression on CD8+ and CD4+ T lymphocytes in patients with RRMS.