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Th2 Cytokine Production (th2 + cytokine_production)
Selected AbstractsProtective effect of curcumin, a Curcuma longa constituent, in early colonic inflammation in rats,DRUG DEVELOPMENT RESEARCH, Issue 6 2009Juan Manuel Sánchez-Calvo Abstract Curcumin, a polyphenol derived from the plant, Curcuma longa, has a variety of pharmacological effects, including chemotherapeutic, anti-inflammatory, antiangiogenic, and antioxidant activities. To gain a better understanding of the effects and mechanisms of action of curcumin on the acute injury caused by intra-colonic administration of acetic acid (AA) in rats, inflammation was assessed by histology and myeloperoxidase activity (MPO; an index of neutrophil infiltration in the mucosa); Th1 and Th2 cytokine production; histological and histochemical analysis of the lesions; nitrite production in colon mucosa; and the expression of iNOS, COX-1 and -2 using Western blotting and inmmunohistochemistry. We also studied the involvement of the p38 MAPK/JNK signalling pathway in the protective effect of curcumin in acute colonic inflammation. Curcumin (50,100,mg/kg/day) reduced the degree of colonic injury, the index of neutrophil infiltration and Th1 cytokine secretion, and increased IL-10 production, reduced colonic levels of nitrites, and reduced COX-2 and iNOS overexpression. A reduction in the activation of p38 and JNK MAPKs was also observed. Thus, we show that the widely used food additive, curcumin reduced the development of AA-induced colitis and alleviated the inflammatory response. Inhibition of MAPK signalling by curcumin could explain the changes on the cytokine Th1/Th2 profile, the reduction of COX-2 and iNOS signaling, as well as the decreased nitrite production in colonic mucosa, suggesting that curcumin may be useful in the treatment of ulcerative colitis. Drug Dev Res, 2009. © 2009 Wiley-Liss, Inc. [source] APRIL (TNFSF13) regulates collagen-induced arthritis, IL-17 production and Th2 responseEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2008Yanping Xiao Abstract A proliferation-inducing ligand (APRIL or TNFSF13) shares receptors with B-cell activation factor of the TNF family (BAFF) on B and T cells. Although much is known about the function of APRIL in B cells, its role in T cells remains unclear. Blocking both BAFF and APRIL suggested that BAFF and/or APRIL contributed to collagen-induced arthritis (CIA); however, the role of APRIL alone in CIA remained unresolved. We show here that, in vitro, our newly generated APRIL,/, mice exhibited increased T-cell proliferation, enhanced Th2 cytokine production under non-polarizing conditions, and augmented IL-13 and IL-17 production under Th2 polarizing conditions. Upon immunization with OVA and aluminum potassium sulfate, APRIL,/, mice responded with an increased antigen-specific IgG1 response. We also show that in APRIL,/, mice, the incidence of CIA was significantly reduced compared with WT mice in parallel with diminished levels of antigen-specific IgG2a autoantibody and IL-17 production. Our data indicate that APRIL plays an important role in the regulation of cytokine production and that APRIL-triggered signals contribute to arthritis. Blockade of APRIL thus may be a valuable adjunct in the treatment of rheumatoid arthritis. [source] Glucocorticoid-induced TNFR family-related protein (GITR) activation exacerbates murine asthma and collagen-induced arthritisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2005Manish Patel Abstract Glucocorticoid-induced TNFR family-related protein (GITR) is expressed at low levels on resting T cells, B cells and macrophages but at high levels on regulatory T cells (Treg). Although GITR expression is up-regulated on CD4+ effector cells upon activation, the role of GITR in Th1 and Th2 cell development is unclear. We report here that activation of GITR signalling by anti-GITR antibody markedly enhanced the induction of both Th1 and Th2 cytokine production by naive CD4+CD25, T cells. Consistent with this observation, anti-GITR antibody significantly enhanced the expression of the key Th1 (T-bet) and Th2 (GATA3) transcription factors in vitro. Administration of anti-GITR mAb in a murine model of arthritis significantly exacerbated the severity and onset of joint inflammation with elevated production of TNF-,, IFN-,, IL-5, and collagen-specific IgG1. Administration of anti-GITR mAb also significantly exacerbated murine allergic airways inflammation with elevated production of OVA-specific IFN-,, IL-2, IL-4, IL-5, and IgE. Finally, we demonstrated that adoptive transfer of CD4+GITR+ T cells effectively abolished airway inflammation induced in SCID mice reconstituted with CD4+GITR, T cells. Our results therefore provide direct evidence that GITR can modulate both Th1- and Th2-mediated inflammatory diseases, and may be a potential target for therapeutic intervention. [source] Lymphoid enhancer factor interacts with GATA-3 and controls its function in T helper type 2 cellsIMMUNOLOGY, Issue 3 2008Mohammad B. Hossain Summary GATA-3 is the master transcription factor for T helper 2 (Th2) cell differentiation and is critical for the expression of Th2 cytokines. Little is known, however, about the nature of the functional molecular complexes of GATA-3. We identified a high-mobility group (HMG)-box type transcription factor, lymphoid enhancer factor 1 (LEF-1), in the GATA-3 complex present in Th2 cells using a Flag-calmodulin-binding peptide (CBP)-tag based proteomics method. The interaction between GATA-3 and LEF-1 was confirmed by co-immunoprecipitation experiments using LEF-1-introduced T-cell lineage TG40 cells. The HMG-box domain of LEF-1 and two zinc finger domains of GATA-3 were found to be important for the physical association. The introduction of LEF-1 into developing Th2 cells resulted in the suppression of Th2 cytokine production. The suppression was significantly lower in the cells into which a HMG-box-deleted LEF-1 mutant was introduced. Moreover, LEF-1 inhibited the binding activity of GATA-3 to the interleukin (IL)-5 promoter. These results suggest that LEF-1 is involved in the GATA-3 complex, while also regulating the GATA-3 function, such as the induction of Th2 cytokine expression via the inhibition of the DNA-binding activity of GATA-3. [source] Piperine inhibits eosinophil infiltration and airway hyperresponsiveness by suppressing T cell activity and Th2 cytokine production in the ovalbumin-induced asthma modelJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2009Seung-Hyung Kim Abstract Objectives This study aimed to investigate the effect of piperine on airway hyper-responsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production, immunoglobulin E and histamine production in a murine model of asthma. Methods Asthma was induced in Balb/c mice by ovalbumin sensitization and inhalation. Piperine (4.5 and 2.25 mg/kg) was orally administered 5 times a week for 8 weeks. At 1 day after the last ovalbumin exposure, airway hyperresponsiveness was determined and samples of bronchoalveolar lavage fluid, lung cells and serum were collected for further analysis. Key findings Piperine-treated groups had suppressed eosinophil infiltration, allergic airway inflammation and airway hyperresponsiveness, and these occurred by suppression of the production of interleukin-4, interleukin-5, immunoglobulin E and histamine. Moreover, polymerase chain reaction products for thymus and activation regulated chemokine from lung cell RNA preparations were decreased in the piperine-treated group compared with control groups, although transforming growth factor-, products were increased in the piperine-treated group. Conclusions The results suggest that the therapeutic mechanism by which piperine effectively treats asthma is based on a reduction of Th2 cytokines (interleukin-4, interleukin-5), eosinophil infiltration, and by marked reduction of thymus and activation regulated chemokine, eotaxin-2 and interleukin-13 mRNA expression (especially transcription of nuclear factor-, dependent genes) in lung tissue, as well as reduced interleukin-4, interleukin-5 and eotaxin levels in bronchoalveolar lavage fluid, and histamine and ovalbumin-specific immunoglobulin E production in serum. [source] Anesthesiologists at work: an increase in pro-inflammatory and Th2 cytokine production, and alterations in proliferative immune responsesACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2006B. Beilin Background:, Anesthesiologists are a population at high risk of alcohol and drug abuse, depression, suicide, and psychiatric hospitalization. The impact of their working milieu on specific immune indices has scarcely been studied, and it is assumed that immune perturbations may contribute to some of the above risks. This study took advantage of an unplanned, 3-month long strike of anesthesiologists, and explored its relations to specific immune measures. Methods:, We assessed induced cytokine production and lymphocytes proliferative responses in blood samples taken from 10 anesthesiologists just before the strike and at its end, after a long period of markedly reduced workload. Results:, The results indicated that the proliferative responses to phytohemagglutinin (PHA) and concanavalin A (Con A) were significantly lower at the end of the strike. At this time point, we observed a significant decrease in the production of interleukin-6 (IL-6), IL-10 and IL1ra levels, and a significant increase in IL-2 production. A strong trend towards a decline in tumor necrosis factor-, (TNF-,) levels was evident, while levels of IL-1, were unchanged. Conclusion:, These findings suggest that the working conditions of anesthesiologists are associated with specific immune alterations, including a shift towards a Th2 cytokines' dominance, and an elevated pro-inflammatory cytokine response. A reduced Th1 profile has been related to increased susceptibility to infections, and high pro-inflammatory cytokine levels were recently proposed as etiological factors in cardiovascular diseases and in depression. [source] Interstitial Cystitis and the Therapeutic Effect of Suplatast TosilateLUTS, Issue 2009Yukio HAYASHI Painful bladder syndrome (PBS)/interstitial cystitis (IC) can be a chronic and debilitating disease characterized by urinary urgency, frequency, and bladder pain, which are often very difficult to treat, regardless of currently-proposed treatments. Suplatast tosilate (IPD-1151T) is an immunoregulator that suppresses Th2 cytokine production, immunoglobulin E (IgE) synthesis, chemical mediator release from mast cells, and eosinophilic recruitment. In a preliminary, open-label clinical study of IPD-1151T in 14 women with IC, treatment with IPD-1151T significantly increased bladder capacity and decreased urinary urgency, urinary frequency, and lower abdominal pain, as measured by the IC symptom index, in patients with non-ulcerative IC. A concomitant reduction in immunological parameters (eosinophils, IgE, and urine T cells) was observed. Also, in basic experimental studies using hydrochloric acid-induced chronic cystitis rats, the oral administration of IPD-1151T (0.1,100 mg/kg/day) for 7 days after the induction of cystitis dose dependently increased the intercontraction intervals and micturition volume. In addition, the infiltration of mast cells and eosinophils into the bladder was suppressed by IPD-1151T. These findings suggest that IPD-1151T could be a new medicine for treating debilitating symptoms, such as bladder pain and urinary frequency in PBS/IC. [source] Cellular responses to Loa loa experimental infection in mandrills (Mandrillus sphinx) vaccinated with irradiated infective larvaePARASITE IMMUNOLOGY, Issue 4 2000Ungeheuer In order to shed light on the mechanisms of antifilarial protective immunity, we investigated the course of experimental loaiosis after vaccination in a nonhuman primate host, Mandrillus sphinx. Six vaccinated (V) mandrills received 50 irradiated L3 while six nonvaccinated (NV) received saline solution on days ,60, ,30 and ,15. All animals were challenged with 100 intact L3 (day 0). Parasitological and immunological status were followed for 9 months. Vaccination delayed the appearance and mean peak of microfilaraemia. Five mandrills (Mf,) were never microfilaraemic (one V mandrill) or microfilaraemic on only one occasion (2 V and 2 NV), the other seven having stable microfilaraemia (Mf+). The cytokine response of peripheral blood mononuclear cells to L3 (L3 Ag) was Th2 dominated, while microfilariae (Mf Ag) elicited a Th0-like response. During vaccination, Th2 cytokine production significantly increased in V mandrills against L3 Ag, as well as Mf Ag, whereas Th1 cytokines decreased. On day 60 postinoculation, cellular proliferation was higher in V mandrills in response to L3 and Mf Ags and PHA-L mitogen. At the end of prepatency (on day 130), mandrills with delayed appearance of microfilaraemia exhibited a high, transient IL-2 and IL-4 secretion in response to L3 Ag. Finally, high anti-Mf Th2 cytokine levels characterized Mf,mandrills not only during prepatency, but also (for IL-5) before immunization. However, the presence of a balanced Th1 anti-L3 response during prepatency in the amicrofilaraemic mandrill suggests its importance in protective immunity. Taken together, our data suggest that Th2 cells and also Th1 components of the antifilarial response, especially to larval antigen, may contribute to parasite elimination. [source] Whole-body UVB (TL-01) or UVA-1 irradiation does not alter the levels of immunomodulatory cytokines in the serum of human volunteersPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 2 2004P. Mcloone Background/Purpose: Ultraviolet (UV) exposure of mammalian skin induces local and systemic immunosuppression. In mice it has been proposed that systemic immunosuppression is mediated by an UV-induced cytokine cascade involving systemic interleukin (IL)-4 and IL-10 and a reduction in IL-12 activity. To investigate whether there was a parallel mechanism in humans we examined the effect of whole-body narrowband ultraviolet B (UVB) (311,313 nm; TL-01) and ultraviolet A (UVA)-1 (340,400 nm) on serum cytokine levels. Methods/Results: In a first study, five male psoriatic subjects were whole-body irradiated with three sessions of a standard UVB (TL-01) phototherapy regimen previously shown to cause downregulation of natural killer cell activity and T helper 1 (Th1) and Th2 cytokine production by peripheral blood mononuclear cells. Enzyme-linked immunoabsorbent assay (ELISA) of sera taken before and after the third session showed no effect of phototherapy on IL-10 and tumour necrosis factor-, (TNF-,). In a second study, five healthy subjects received three whole-body exposures of UVB (TL-01) and five other healthy subjects received three exposures of UVA-1 on alternate days (total 22 J/cm2). Blood samples were taken before the first irradiation and at 0, 4, 8, 12, 14, 24 and 48 h after the third irradiation. The sera were subsequently analysed for IL-10, IL-12, IL-8, IL-1, and TNF-,, by ELISA. The levels of IL-1, and TNF-, were below detection limits (<5 pg/ml), while no significant change in the levels of IL-10, IL-12 or IL-8 was detected as a result of either TL-01 or UVA-1. Conclusion: It seems unlikely that a modulation in these circulating cytokines assessed in this study accounts for systemic UV-induced immunosuppression in human subjects. [source] Gender differences in transcriptional regulation of IL-5 expression by bronchial lymph node cells in a mouse model of asthmaRESPIROLOGY, Issue 4 2010Kana WADA ABSTRACT Background and objective: The severity of asthma after puberty is higher in women than in men. Increased numbers of eosinophils in the airways of female mice after antigen challenge was associated with increased levels of T helper (Th)2 cytokines at the site of inflammation, and in human and mouse studies, the profile of cytokines produced by immune cells from women showed greater Th2 predominance. The aim of this study was to investigate gender differences in the development of Th2 immune responses. Methods: Male and female C57BL/6 mice were sensitized with ovalbumin. Cells prepared from bronchial lymph nodes were cultured in the absence or presence of ovalbumin. Cytokine concentrations in the culture supernatants were measured, and IL-5 and GATA-binding protein 3 (GATA-3) gene expression were evaluated. T-cell subsets were analysed using specific surface markers. Results: The concentrations of IL-4, IL-5, IL-13 and IL-10, but not interferon-, or transforming growth factor-,1, were higher in cell supernatants from female mice than in those from male mice. IL-5 and GATA-3 gene expressions were higher in cells from women than in cells from men. The numbers of CD3+CD4+T1/ST2+ cells, but not CD3+CD4+ or CD4+CD25+ cells, were significantly higher in cells from women than in cells from men. Conclusions: Greater antigen-induced Th2 cytokine production by bronchial lymph node cells from female mice was associated with enhanced Th2 cell differentiation and increased expression of the Th2-specific transcription factor, GATA-3. [source] Effects of Th2 pulmonary inflammation in mice with bleomycin-induced pulmonary fibrosisRESPIROLOGY, Issue 6 2008Hirokuni HIRATA Background and objective: Leucocytes, especially lymphocytes and neutrophils, as well as alveolar macrophages, that infiltrate into the lung are involved in the development of pulmonary fibrosis. However, the role of T helper (Th)2-type inflammation, mediated by Th2 cells and eosinophils, in fibrosis remains unknown. Transgenic mice deficient in the transcriptional repressor, Bcl6, display an attenuation of Th2 cytokine production. We studied the effects of Th2-type pulmonary inflammation on bleomycin-induced pulmonary fibrosis using Bcl6 transgenic mice. Methods: Bleomycin was administered to ovalbumin (OVA)-sensitized Bcl6 transgenic and wild-type mice by intratracheal instillation during sequential OVA antigen challenge. Concentrations of transforming growth factor-,1 in the BAL fluid were measured 2 weeks after bleomycin administration. At the same time lung tissue was examined histopathologically, and homogenized to assess collagen levels and Th1/Th2 cytokine mRNA expression. Results: Although OVA-sensitized, bleomycin-treated Bcl6 transgenic mice had markedly lower numbers of eosinophils in both BAL and lung tissue compared with OVA-sensitized, bleomycin-treated wild-type mice, the development of pulmonary fibrosis in response to bleomycin was similar in Bcl6 transgenic mice and wild-type mice. Conclusion: These results suggest that Th2-dominant inflammation in the lung is not essential for the development of bleomycin-induced pulmonary fibrosis. [source] Endotoxin-Induced Myeloid-Derived Suppressor Cells Inhibit Alloimmune Responses via Heme Oxygenase-1AMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009V. De Wilde Inflammation and cancer are associated with impairment of T-cell responses by a heterogeneous population of myeloid-derived suppressor cells (MDSCs) coexpressing CD11b and GR-1 antigens. MDSCs have been recently implicated in costimulation blockade-induced transplantation tolerance in rats, which was under the control of inducible NO synthase (iNOS). Herein, we describe CD11b+GR-1+MDSC-compatible cells appearing after repetitive injections of lipopolysaccharide (LPS) using a unique mechanism of suppression. These cells suppressed T-cell proliferation and Th1 and Th2 cytokine production in both mixed lymphocyte reaction and polyclonal stimulation assays. Transfer of CD11b+ cells from LPS-treated mice in untreated recipients significantly prolonged skin allograft survival. They produced large amounts of IL-10 and expressed heme oxygenase-1 (HO-1), a stress-responsive enzyme endowed with immunoregulatory and cytoprotective properties not previously associated with MDSC activity. HO-1 inhibition by the specific inhibitor, SnPP, completely abolished T-cell suppression and IL-10 production. In contrast, neither iNOS nor arginase 1 inhibition did affect suppression. Importantly, HO-1 inhibition before CD11b+ cell transfer prevented the delay of allograft rejection revealing a new MDSC-associated suppressor mechanism relevant for transplantation. [source] Inhibition of human allergic T-helper type 2 immune responses by induced regulatory T cells requires the combination of interleukin-10-treated dendritic cells and transforming growth factor-, for their inductionCLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2006I Bellinghausen Summary Background In grass pollen-allergic individuals, T cell anergy can be induced by IL-10-treated dendritic cells (IL-10-DC) resulting in the suppression of T helper type 1 (Th1) as well as Th2 cells. This study was performed to analyse whether such IL-10-DC-treated T cells are able to act as regulatory T cells (Treg) suppressing the function of other T cells in the periphery. As transforming growth factor (TGF)-, is also a potential inducer of Treg, we additionally analysed the inhibitory capacity of TGF-,-treated T cells in this system. Materials and Methods Freshly isolated CD4+ or CD4+CD25, T cells from grass pollen-allergic donors were stimulated with autologous mature monocyte-derived allergen-pulsed DC in the presence or absence of T cells previously cultured with IL-10-DC- and/or TGF-,. Results Anergic T cells induced by allergen-pulsed IL-10-treated DC or allergen-pulsed DC and TGF-, enhanced IL-10 production and strongly inhibited IFN-, production of freshly prepared peripheral CD4+ or CD4+CD25, T cells while proliferation and Th2 cytokine production were only slightly reduced. The combination of allergen-pulsed IL-10-treated DC and TGF-, had an additional effect leading to a significant suppression also of Th2 cytokine production and proliferation. Suppression was not antigen-specific and was mainly mediated by cell-to-cell contact and by the molecule-programmed death-1 and only partially by CTLA-4, TGF-, and IL-10. Conclusion These data demonstrate that regulatory T cells that also suppress Th2 cytokine production are induced by two signals: TGF-, and IL-10-DC. This is of importance for the regulation of allergic immune responses and might be exploited for future therapeutic strategies for allergic diseases. [source] Expression and function of the ST2 gene in a murine model of allergic airway inflammationCLINICAL & EXPERIMENTAL ALLERGY, Issue 10 2002K. Oshikawa Summary Background We have recently reported that soluble ST2 protein levels are elevated in the sera of patients with asthma, and correlate well with the severity of asthma exacerbation. However, the role, function, and kinetics of soluble ST2 expression in asthma remain unclear. Objective The objective of the present study was to clarify the function and kinetics of soluble murine (m) ST2 expression in a murine asthma model. Methods We analyzed the kinetics of gene and protein expression of mST2 in sera or lung tissue after allergen (ovalbumin; OVA) challenge in a murine model of allergic airway inflammation, the effects of mST2 protein on OVA-induced Th2 cytokine production in vitro from splenocytes of sensitized mice, and the effects of soluble mST2 on Th2-dependent allergic airway inflammation by in vivo gene transfer of mST2. Results Serum mST2 protein levels increased to the maximal level 3 h after the allergen challenge, before serum IL-5 levels peaked. The mRNA expression of mST2 in lung tissue was induced after the allergen challenge, while that in the spleen was constitutively detected. Furthermore, pre-treatment with mST2 protein significantly inhibited the production of IL-4 and IL-5, but not IFN-,, from OVA-stimulated splenocytes in vitro, and intravenous mST2 gene transfer resulted in a drastic reduction in the number of eosinophils and in the levels of IL-4 and IL-5 in bronchoalveolar lavage fluid, compared with those in response to transfer of non-coding plasmid vector or of lipid alone. Conclusion These results suggest that increases in endogenous mST2 protein after allergen exposure may modulate Th2-mediated airway inflammation, and that in vivo gene transfer of mST2 can be applicable to use in a novel immunotherapy for allergic diseases. [source] T helper 1 (Th1)/Th2 cytokine expression shift of peripheral blood CD4+ and CD8+ T cells in patients at the post-acute phase of strokeCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2008G. L. Theodorou Summary 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)-,] 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-, 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-,-/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. [source] Circulating ,/, T lymphocytes from systemic sclerosis (SSc) patients display a T helper (Th) 1 polarizationCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2001R. Giacomelli Systemic sclerosis (SSc) is a connective tissue disease in which immune system activation is evidenced by high levels of different cytokines in the sera and/or in the supernatants of cultured peripheral blood mononuclear cells (PBMC) and by the presence of specific autoantibodies. ,/, T cells accumulate in the lung and the skin of SSc patients suggesting their potential role in the development and maintenance of the disease. The aim of this study was to assess cytokine production and cytotoxic activity of circulating ,/, T lymphocytes obtained from SSc patients and to evaluate their potential role during this disorder. Our results showed that both the proportion and the absolute number of IFN- ,,/, -producing cells (i.e. displaying a Th1 polarization) in SSc was significantly higher than either the proportion and the absolute number of IL-4 ,/, -producing cells in SSc or the proportion and the absolute number of IFN- ,,/, -producing cells in healthy controls (P < 0·05 for both groups). Furthermore, the cytotoxic activity of enriched ,/, T cells was significantly increased in SSc patients compared with controls. The results concerning the V,1+ T cell subset paralleled those of total ,/, T lymphocytes. In contrast, ,/, T cells from SSc and control subjects displayed Th2 cytokine production. All these findings were independent of both disease subset and clinical status. Our data demonstrate that, although SSc is generally considered a Th2 autoimmune disease, Th1 polarization of ,/, T cells and an increase in their cytotoxic activity is observed in SSc, suggesting that ,/, T cells could have a relatively autonomous role in the pathogenesis in this disease. [source] | ||||||||||