T helper 1 (Th1)/Th2 cytokine expression shift of peripheral blood CD4+ and CD8+ T cells in patients at the post-acute phase of stroke

Local humoral and cellular immune responses modulate the inflammatory processes involved in the development of atherosclerotic lesions, as well as in the evolution of brain infarcts in stroke patients. The role of systemic adaptive immunity on the progression of such disease manifestations is less clear. In the current study, we evaluated the percentages of T helper 1 (Th1) [interleukin (IL)-2, interferon (IFN)-gamma] and Th2 (IL-4, IL-10) cytokine-producing peripheral blood CD4+ and CD8+ T cells in 23 patients with a history of ischaemic stroke (IS) at the chronic stable phase of the disease (median post-stroke time 34.5 months). Seven stroke-free individuals matched for age and vascular risk factors (matched controls, MC) were collected for comparison. To measure cytokine values at baseline and after stimulation, we used a flow cytometry method of intracellular cytokine staining. Intrinsic Th1 and Th2 cytokine production in unstimulated T cells was negligible in all study participants. Following mitogenic stimulation with phorbol 12-myristate13-acetate/ionomycin, both the IS and the MC groups exhibited a similarly strong Th1 response; IL-2 production predominated in the CD4+ T cells and IFN-gamma in the CD8+ T cells. However, when measuring the Th2 cytokine-production capacity post-stimulation, a significant increase in the percentage of IL-4-producing T cells was observed in the IS groups, compared with the MC group, resulting in a significantly lower ratio of IFN-gamma-/IL-4-producing T cells. No such Th2 enhancement could be confirmed for the case of IL-10. We propose that in IS patients there is a systemic shift of the immune system towards Th2 responses at the late post-acute phase of stroke.     

Th1 cytokine pattern in sarcoidosis is expressed by bronchoalveolar CD4+ and CD8+ T cells

The pathogenesis of pulmonary sarcoidosis has been related to an increased production of Th1-like cytokines. However, cytokine expression in sarcoidosis has not been systematically studied at a single-cell level. We therefore investigated the expression of IL-2, IL-4, IL-13, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) intracellularly in bronchoalveolar lavage (BAL) and peripheral blood CD3+ T lymphocytes from patients with pulmonary sarcoidosis (radiologic stage II-III, n = 8) and normal controls (n = 9) by flow cytometry. In contrast to IL-4 and IL-13, the percentage of T lymphocytes expressing intracellular IL-2 (49.3 +/- 21.3% versus 14.5 +/- 15.6%), IFN-gamma (75.5 +/- 14.9% versus 32.6 +/- 18.7%) and TNF-alpha (68.3 +/- 18.7% versus 36.8 +/- 20.8%) was significantly higher in patients with sarcoidosis than in normal controls (each P < 0.005). In contrast to BAL lymphocytes, expression of these cytokines in peripheral blood lymphocytes did not differ between patients with sarcoidosis and normal controls. Close correlations were observed between the percentages of BAL lymphocytes expressing intracellular IL-2, IFN-gamma and TNF-alpha, but not for IL-4 or IL-13. Analysis of the expression of these cytokines in T lymphocyte subsets revealed IL-2, IFN-gamma, and TNF-alpha in CD4+ as well as CD8+ T lymphocytes, suggesting a contribution of TC1 cells to the production of proinflammatory cytokines in sarcoidosis. We conclude that a Th1-like cytokine pattern can be observed in CD4+ as well as in CD8+ BAL T lymphocytes in patients with pulmonary sarcoidosis.     

Th1 and Th2 cells help CD8 T-cell responses

Help from CD4 T cells is often important for the establishment of primary and memory CD8 T-cell responses. However, it has yet to be determined whether T helper polarization affects the delivery of help and/or whether responding CD8 T cells helped by Th1 or Th2 cells express distinct effector properties. To address these issues, we compared CD8 T-cell responses in the context of Th1 or Th2 help by injecting dendritic cells copulsed with the major histocompatibility complex class I-restricted OVA peptide plus, respectively, bacterial or helminth antigens. We found that Th2 cells, like Th1 cells, can help primary and long-lived memory CD8 T-cell responses. Experiments in interleukin-12 (IL-12)-/- and IL-4-/- mice, in which polarized Th1 or Th2 responses, respectively, fail to develop, indicate that the underlying basis of CD4 help is independent of attributes acquired as a response to polarization.     

Increased interleukin-17 production both in helper T cell subset Th17 and CD4-negative T cells in human immunodeficiency virus infection

Interleukin (IL)-17 is produced mainly by activated CD4(+) T cells, currently known as Th17. Human immunodeficiency virus (HIV) pathogenesis leads to CD4(+) T cell depletion. This is the first report of IL-17 in HIV infection. We assessed IL-17 expression in the CD4(+) T cells (Th17) of 40 asymptomatic HIV-infected treatment-naive patients compared with 40 HIV-seronegative volunteers. Peripheral blood mononuclear cells (PBMCs), with/without phorbol myristate acetate (PMA)/ionomycin stimulation, were stained with CD3, CD4, IL-17, and interferon (IFN)-gamma antibodies and analyzed by four-color flow cytometry. Both groups had comparable baseline data, except for age (mean+/-SD): 36 +/- 9 versus 30 +/- 9 yr (p= 0.001), CD4(+) T cell counts (median): 218 versus 623 cells/microL (p < 0.0001), CD8(+) T cell counts (median): 875.5 versus 382.5 cells/microL ((p) < 0.0001), and CD4(+)/CD8(+) cell ratios (median): 0.225 versus 1.45 (p< 0.0001). Without stimulation, the percentages of IL-17(+) CD3(+) CD4() and IL-17(+) CD3(+) CD4() cells among HIV-seropositive and -seronegative volunteers (median) were as follows: 0.68 versus 0.12% (p< 0.0001) and 0.92 versus 0.09% (p< 0.0001), respectively. With PMA/ionomycin stimulation, the percent IL-17 expression in CD4(+) cells (median) was 1.45 versus 0.65 (p< 0.0001) and in CD4() T cells it was 1.0 versus 0.12 (p< 0.0001). In conclusion, HIV infection is associated with a significant increase in IL-17 production in both CD4(+) and CD4() T cells in peripheral blood. IL-17 expression was further inducible by PMA/ionomycin stimulation in vitro only in CD4(+) T cells. The roles of IL-17 and Th17 in HIV viral replication and immunopathogenesis are under further investigation.     

Flow cytometric detection of intracellular cytokines in peripheral blood of HIV-1 infected Thai children.

The objective of this study was to determine changes in Th1/Th2 cytokine production at the cellular level which occur during the progression of HIV-1 subtype E infection in Thai children born to HIV-1 subtype E infected mothers. Mitogen stimulated whole blood cultures from 12 uninfected and 27 HIV-1 subtype E infected Thai children were stained intracellularly with fluorescein labelled monoclonal antibodies against Interleukin (IL)-2 and IFN-gamma (Th1 cytokines) and IL-4 (Th2 cytokine). Additionally, co-staining of CD4+ and CD8+ T cells was performed. Results were analyzed by two and three color flow cytometry. The percentage of IFN-gamma expressing cells in CD4+ T cells was increased in HIV-1 subtype E infected Thai children with mild and moderate immunosuppression (Immunological categories 1 + 2, Centers for Diseases Control and Prevention (CDC) staging system, 1994). The percentages of IFN-gamma expression was continuously enhanced accompanied by remaining preserved in the proportion of IL-2 producing T cells in HIV-1 subtype E infected Thai children with severe immunosuppression (Immunological category 3, CDC staging system, 1994). The percentages of IFN-gamma expression was continuously augmented whereas the proportion of IL-2 producing T cells remained unchanged in HIV-1 subtype E infected Thai Children with severe immunosuppression (immunological category 3, CDC staging system, 1994). The percentage of Th2 cytokine producing cells within the CD4+ ad CD8+ T cells increased in HIV-1 subtype E infected individuals and showed a significant difference in HIV-1 subtype E infected Thai children with AIDS compared with uninfected infants. These results suggest that in vertically acquired HIV-1 infection with severe immunosuppression, the percentages of IL-2 producing CD4+ T cell was consistent but the percentages of IL-4 and IFN-gamma producing cell were increased. Similar results were found for CD8+ T cells in which IL-4 producing cells were increased in conjunction with a remaining in the number of IL-2 producing cells in HIV-1 subtype E infected Thai children. Thus, changes in the Th1 and Th2 cytokine pattern during HIV-1 infection may contribute to the prognosis of HIV disease in children.     

Differential expression of the chemokine receptors by the Th1- and Th2-type effector populations within circulating CD4+ T cells

The in vitro studies have proposed that human Th1 cells favor expression of CXCR3 or CCR5, whereas Th2 cells favor CCR3 and CCR4. In this study, the in vivo relevance of expression of these chemokine receptors on Th cells was investigated in patients with atopic dermatitis (AD) as the Th2-dominated disorder and nonatopic normal individuals. Flow-cytometric analysis using monoclonal antibodies against CXCR3, CCR5, CCR3, and CCR4 disclosed that a substantial proportion of memory (CD45RO+) CD4+ T cells in the blood of AD and normal patients expressed CXCR3, CCR5, or CCR4, but expression of CCR3 on these cells was negligible. Stimulation studies combined with intracellular cytokine staining revealed that the cells capable of producing Th2 cytokines, such as interleukin-4 (IL-4), IL-5, and IL-13, were restricted to the CCR4-expressing population within memory CD4+ T cells. Concerning Th1 cytokine production, interferon-gamma (IFN-gamma)-producing cells resided exclusively in CXCR3-expressing memory CD4+ T cells, although IFN-gamma production was found in both memory CD4+ T cells with and without CCR5 expression. We observed that CCR4-expressing memory CD4+ T cells in the blood were more increased in AD patients as compared with normal patients, whereas CXCR3-expressing memory CD4+ T cells were present in a lower frequency in AD than seen in normal patients. These results suggest that CXCR3 and CCR4, but not CCR5 or CCR3, appear to serve as the useful markers for identification of circulating Th1 and Th2 effector populations.     

Efficient replication of human immunodeficiency virus type 1 in cytokine induced CD 4+ T helper 1 (Th 1)- and Th 2-type conditions]

Potent stimuli for CD 4+ T cell differentiation are cytokines. Among them, IL-12 or IL-4 induce naive CD 4+ T cells to Th 1 or Th 2 cells, respectively. In this study we found that macrophage-tropic (M-tropic) HIV-1 strains more efficiently replicated in interleukin 12 (IL-12) induced T helper 1 (Th 1)-type culture derived from normal CD 4+ T cells than T-cell-line-tropic (T-tropic) strains did. In contrast, T-tropic strains preferentially infected IL-4 induced Th 2-type culture derived from same donor CD 4+ T cells. Additional studies using chimeric viruses demonstrated that the V 3 region of gp 120 was the principle determinant for this efficient replication. It was also isolated T-tropic viruses from an acutely infected patient who had been evidenced as severe CD 4 depletion during short time course. These results indicate that HIV-1 isolates exhibit differences in the ability to infect CD 4+ T cell subset such as Th 1 or Th 2 cells, and that this difference may partly correlate with the viral pathogenesis. The findings suggest that immunological condition is one of the factors responsible for inducing selection of HIV-1 strains.     

CD31 (PECAM-1) is a differentiation antigen lost during human CD4 T-cell maturation into Th1 or Th2 effector cells.

The CD31 antigen (PECAM-1) has been reported to be a stable marker for a human CD4 T-cell subpopulation unable to produce interleukin-4 (IL-4). We show here that CD31 expression is not stable inasmuch as CD4 T-cell lines and clones derived from cell-sorted neonatal CD31+ cells lose CD31 upon repetitive cycles of stimulation and IL-2 expansion. Moreover, various cytokines (IL-1 alpha, IL-4, IL-6, transforming growth factor-beta) fail to reinduce CD31 on CD31- clones. Whereas all CD31+ CD4 T cells rapidly express high levels of the CD45RO antigen and down-regulate the L-selectin antigen after priming, CD31 disappears more slowly because only part of the cells lose CD31 expression upon each cycle of stimulation. Loss of CD31 reflects a functional maturation of CD45RO+ cells since, in a system which favours the development of Th2 effectors, IL-4 is produced by CD31- but not CD31+ effector T cells, whereas interferon-gamma is produced by both types of cells. However, CD31 is not a Th1 marker since it is not expressed on several Th1 antigen-specific clones. We conclude that CD31 is a maturation marker expressed on the great majority of naive CD45RO- CD4 T cells and on a subset of CD45RO+ CD4 T cells that are at an intermediate stage of maturation.     

Massive production of Th2 cytokines by human CD4+ effector T cells transiently expressing the natural killer cell marker CD57/HNK1.

We have reported previously that uncommitted human CD4+ CD45RO- T cells default to the T-helper type 1 (Th1) pathway, if they are costimulated by anti-CD3 plus anti-CD28 monoclonal antibodies (mAb). In contrast, 5% of the uncommitted T cells differentiate into Th2 cells, if they are stimulated by anti-CD28 plus interleukin-2 (IL-2) in the absence of T-cell receptor (TCR) signals. The anti-CD28/IL-2-induced proliferation (and the resulting Th2 commitment) was not affected by neutralizing anti-IL-4 mAb, suggesting a non-conventional IL-4-independent Th2 differentiation pathway. Here we report that the respective CD4+ Th2 cells (but not the Th1 cells) coexpressed the natural killer (NK) cell marker HNK1/CD57. Expression of CD57 on Th2 cells required CD28 stimulation, and was suppressed by CD3/TCR signals. However, Th2 effector cells displayed a TCR V beta-chain usage comparable to that of committed Th1 cells (with V beta 8 dominating). Our data suggest that expression of CD57 on human CD4 T cells may be associated with defined stages of Th2 cell activation/differentiation, and may not necessarily characterize a separate T-cell lineage. The induction of cytokine production and B-cell helper function in both Th1 and Th2 populations required CD3/TCR signalling in costimulation with anti-CD28 or IL-2. Importantly, anti-CD28/IL-2-primed Th2 cells readily secreted IL-4 and induced IgE production by surface IgE- B cells in response to the first TCR signal and independent of previous contact with IL-4. Therefore, CD4+ CD57+ T cells responded comparably to murine CD4+ NK1.1+ T cells, which are critical for the development of Th2/IgE immune responses in vivo. The possible role of human CD4+ CD57/HNK1+ Th2-like cells in cancer, infection and allergy is discussed.     

灭活HIV-1颗粒对人CD4+T细胞活化和全血Th1/Th2细胞因子分泌的影响

目的：体外研究AT-2灭活的HIV-1颗粒对人CD4+T细胞活化和全血(whole blood，WB) Th1/Th2细胞因子分泌的影响。方法:AT-2灭活HIV-1ⅢB型病毒颗粒，运用ELISA法测定所制备的灭活病毒中p24抗原的含量，按照1/500、1/50和1/5 (V/V)的浓度加入到WB中，以植物血凝素(phytohemagglutinin，PHA)组为阳性对照；24 h后，收集WB培养上清，运用流式微球分析法（cytometric bead array，CBA）检测WB分泌Th1 (IL-2、IFN-γ和TNF-α)和Th2 (IL-4、IL-6和IL-10)细胞因子水平；同时运用免疫荧光抗体染色技术结合流式细胞术检测WB中CD4+T细胞早期活化标记分子CD69的表达百分率。结果:我们所制备的灭活病毒中p24抗原的含量为85.5 μg/L；24 h后，空白对照组中，CD4+T细胞CD69的表达百分率为(1.62±0.63)%，PHA组为(38.82±6.00)%，HIV-1(1/500)组为(3.83±1.07)%，HIV-1(1/50)组为(5.94±0.85)%，HIV-1(1/5)组为(9.30±1.22)%；空白对照组WB培养上清中细胞因子主要为IL-6和TNF-α，PHA组中Th1和Th2细胞因子全部升高，3个浓度的HIV-1组中Th1和Th2细胞因子也全部升高。结论:AT-2灭活的HIV-1ⅢB颗粒能够明显引起WB中CD4＋T细胞活化，并上调WB培养上清中Th1和Th2细胞因子的水平，其机制可能是除了HIV-1病毒蛋白的作用外，HIV-1出胞时，许多宿主细胞来源的免疫分子整合到病毒颗粒包膜中，而模拟抗原提呈细胞，从而产生免疫调节作用。     

HIV-1 transgenic rat CD4+ T cells develop decreased CD28 responsiveness and suboptimal Lck tyrosine dephosphorylation following activation

Impaired CD4+ T cell responses, resulting in dysregulated T-helper 1 (Th1) effector and memory responses, are a common result of HIV-1 infection. These defects are often preceded by decreased expression and function of the alpha/beta T cell receptor (TCR)-CD3 complex and of co-stimulatory molecules including CD28, resulting in altered T cell proliferation, cytokine secretion and cell survival. We have previously shown that HIV Tg rats have defective development of T cell effector function and generation of specific effector/memory T cell subsets. Here we identify abnormalities in activated HIV-1 Tg rat CD4+ T cells that include decreased pY505 dephosphorylation of Lck (required for Lck activation), decreased CD28 function, reduced expression of the anti-apoptotic molecule Bcl-xL, decreased secretion of the mitogenic lympokine interleukin-2 (IL-2) and increased activation induced apoptosis. These events likely lead to defects in antigen-specific signaling and may help explain the disruption of Th1 responses and the generation of specific effector/memory subsets in transgenic CD4+ T cells.     

Early Th1/Th2 cell polarization in the absence of IL-4 and IL-12: T cell receptor signaling regulates the response to cytokines in CD4 and CD8 T cells.

Differentiation of developing T cells into the type 1 (IFN-gamma-producing) or type 2 (IL-4-producing) subsets is a central theme of immune regulation. The balance of IL-4 and IL-12 present during T cell activation has been considered the major influence on type 1 versus type 2 development. Here we show that CD4 T cells can become biased towards type 1 or type 2 phenotypes during their initial activation in the absence of IL-4 or IL-12. This type of regulation is dependent on the balance of MAPkinase, protein kinase C, and calcineurin signaling after TCR engagement. Later maturation of Th1 or Th2 effectors is dependent on IL-12 or IL-4. However Tc1 CD8 effector development is independent of IL-12, and Tc2 cell generation requires both appropriate TCR signals and IL-4 early in effector development. Using an altered peptide ligand to stimulate TCR transgenic T cells, we show that altered signaling regulates the numbers of CD8 cells capable of developing into Tc2 effectors, and also their responsiveness to IL-4. Together, the results support a two-stage model of differentiation in which intermediate cells biased towards the type 1 or type 2 pathways after activation, are subsequently matured in response to IL-12 or IL-4, respectively.     

Antiretroviral therapy-induced dominant interleukin-2 HIV-1 Gag CD4+ T cell response: evidence of functional recovery of HIV-1-specific CD4+ T cells

Prolonged antiretroviral treatment (ART) significantly changes the cytokine secretion capacities of HIV-1-specific T cells. However, it is unclear whether these changes result from decreased viremia or they correspond to true functional recovery of viral-specific immune response. To study this issue, we analysed the quantitative and qualitative differences of HIV-1-specific and polyclonal CD4+ and CD8+ T cells between 26 naive and 52 treated individuals. HIV-1 Gag and staphylococcal enterotoxin B (SEB)-reactive T cells were determined by flowcytometric intracellular secretion of IFN-γ or/and ΙL-2. ART resulted in increase of single IL-2 and decrease of single IFN-γ-secreting HIV-1 CD4+ T cells, while both cytokines secreting HIV-1 CD4+ T cells were presented in comparable frequencies in both groups. Viral loads correlated negatively with single IL-2 and positively with single IFN-γ-secreting HIV-1 CD4+ cells. Single IL-2 HIV-1 CD4+ T cells correlated positively with both cytokines secreting polyclonal CD8+ T cells. By qualitative analysis, a dominant IL-2 HIV-1 CD4+ T cell response (> 70% single IL-2) was identified only in ART suppressed patients, who also generated increased dual specific polyclonal CD8+ T cells. Polyfunctional HIV-1 CD4+ T cell responses were detected even in naive individuals with high viremia. In conclusion, the presence of dominant IL-2 HIV-1 CD4+ T cell response, associated with increased CD8+ T cells capable to produce IL-2, indicates that the recovery of HIV-1-specific CD4+ T cell functionality under ART is a feasible goal. Furthermore, polyfunctional HIV-1 CD4+ T cell responses seem not to be directly involved in viral replication control.     

Th1/Th2 profile in peripheral blood in atopic cough and atopic asthma

BACKGROUND: Eosinophilic tracheobronchitis with cough hypersensitivity, abbreviated as atopic cough, is an important cause of chronic cough. The reason for the absence of airway hyper-responsiveness is unknown, differing from asthma, a Th2 cytokine-mediated disorder. OBJECTIVE: To compare the type 1 helper T cell (Th1)/Th2 balance in the peripheral blood from subjects with atopic cough and atopic asthma, we assessed the intracellular cytokine production at the single-cell level. METHODS: Thirty-six subjects (10 patients with atopic cough, 18 with atopic asthma, and eight control subjects) were included. Intracellular IL-4 and IFN-gamma were detected in CD4+ T cells by flow cytometry. RESULTS: A significantly lower ratio of IFN-gamma-/IL-4-producing CD4+ T cells after phorbol 12-myristate acetate/ionomycin stimulation was found in patients with atopic cough and atopic asthma compared with normal subjects. In comparison between atopic patients, the ratio of IFN-gamma-/IL-4-producing cells was significantly higher in atopic cough than in atopic asthma. However, the proportion of IL-4-producing CD4+ T cells was significantly higher in patients with atopic asthma than in normal control subjects and no significant difference was detected between patients with atopic cough and normal subjects. No significant difference in the proportion of IFN-gamma-producing cells was found between the subjects. Overall, the total IgE levels were positively correlated to the IL-4-producing cells and inversely correlated to the ratio of IFN-gamma-/IL-4-producing cells. CONCLUSION: These results show the lower degree of Th2 cytokine predominance in atopic cough compared with atopic asthma and suggest the relation between the Th1/Th2 balance and atopic status.     

Effect of pregnancy and human immunodeficiency virus infection on intracellular interleukin-2 production patterns

Human immunodeficiency virus type 1 (HIV-1) infection decreases the production of interleukin-2 (IL-2) from CD4+ and CD8+ T cells. Recombinant IL-2 (rIl-2) has been given to HIV-infected individuals to generate significant increases in CD4+ T-cell counts. There are limited data regarding the effects of pregnancy and HIV infection on IL-2 production in humans. To investigate the effects of human pregnancy, HIV infection, and HIV therapy on IL-2 production, we evaluated 61 women. Intracellular IL-2 production by CD4+ T cells from nonpregnant HIV-infected women was significantly lower than in that in uninfected women (45% +/- 8% versus 52% +/- 8%, P = 0.04). In contrast, there was no difference in levels of intracellular IL-2 production between HIV-infected and uninfected pregnant women. These observations suggest that pregnancy may down-regulate IL-2 production regardless of HIV infection status. Future studies should evaluate IL-2 production patterns in larger cohorts of women so that the physiological significance of IL-2 down-regulation in pregnancy can be further evaluated. This information is essential to assess the possible use of IL-2 supplementation therapy as a means of enhancing immune responses among HIV-infected pregnant women.     

Beneficial effect of co-polymer 1 on cytokine production by CD4 T cells in multiple sclerosis

Multiple sclerosis (MS) has been associated with an imbalance in the T helper type 1 (Th1) and Th2 subsets. We investigated, at the single-cell level, the synthesis of pro-inflammatory cytokines by CD4 and CD8 T cells from MS patients. We report the relationship between priming of CD4 and CD8 T cells for interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) and disease evolution in MS patients, clinically subdivided into relapsing-remitting MS (RRMS) in remission, RRMS in relapse, or chronic progressive MS (CPMS). Moreover, we report the in vivo influence of co-polymer 1 (COP) treatment on the pattern of cytokine producers in RRMS patients. We show that the frequency of CD4 T cells primed for TNF-alpha synthesis increased in all stages of MS, including RRMS remitting, and was normalized to control values in COP-treated patients (43.2 +/- 11.8% in treated patients versus 47 +/- 7.3% in RRMS remitting versus 40.3 +/- 8% in controls). In addition, a significant decrease in the frequency of CD4 T cells primed for IL-2 was found in COP-treated patients as compared to the other groups of patients, reaching values below that of controls (59.1 +/- 9.9% in treated patients versus 70 +/- 11.6% in RRMS remitting versus 67.1 +/- 7.4% in controls). Unexpectedly, COP-treated patients also showed a significantly decreased priming for IFN-gamma at the CD4 T-cell level (9.1 +/- 3.4% in treated patients versus 18.8 +/- 0.6.4% in RRMS remitting versus 15.4 +/- 4.7% in controls), but not at the CD8 T-cell level. This bystander suppression on the inflammatory cells should be considered in the monitoring of MS patients submitted to COP treatment, in order to evaluate better its clinical efficacy.     

Leishmania donovani-reactive Th1- and Th2-like T-cell clones from individuals who have recovered from visceral leishmaniasis.

Infections in humans by Leishmania donovani parasites can result in a fatal disease, visceral leishmaniasis (VL), or in a self-limiting asymptomatic infection. In murine models of the infection employing Leishmania major, the course of the disease can be directed into a VL-like syndrome by interleukin-4 (IL-4)-producing Th2 cells, or cure may result by Th1 cells secreting gamma interferon (IFN-gamma). The present study examined the potential of human T cells to generate Th1 or Th2 responses to L. donovani. The profiles of IFN-gamma, IL-4, and lymphotoxin secretion after antigen stimulation were analyzed in a panel of L. donovani-reactive CD4+ human T-cell clones generated from individuals who had recovered from VL after antimonial treatment. Two of the T-cell clones produced large amounts of IL-4 without production of IFN-gamma, seven clones produced both IFN-gamma and IL-4, and eight produced only IFN-gamma. This is the first report of a Th1- and Th2-type response in human leishmaniasis. These results suggest that in analogy with murine models, there is a dichotomy in the human T-cell response to L. donovani infections. Preferential activation of IL-4-producing Th2-like cells may be involved in the exacerbation of human VL, whereas activation of IFN-gamma-producing Th1 cells may protect the host from severe disease. Identification of leishmanial antigens activating one or the other type of T cells will be important in the development of vaccines against leishmaniasis.