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CD4+CD25+ T Cells (cd4+cd25+ t + cell)
Kinds of CD4+CD25+ T Cells Selected AbstractsA Possible Role of CD4+CD25+ T Cells as Well as Transcription Factor Foxp3 in the Dysregulation of Allergic RhinitisTHE LARYNGOSCOPE, Issue 5 2007Geng Xu MD Abstract Background: Allergic rhinitis (AR) is a Th2 predominant disease, and its pathogenic mechanism is still poorly understood. CD4+CD25+ T cells account for approximately 5% to 10% peripheral CD4+ T cells and has been shown to regulate the activation of effector T cells in the periphery. The activity of CD4+CD25+ T cells is associated with the transcription factor Foxp3. The present study aimed to evaluate the possible role of CD4+CD25+ T cells as well as Foxp3 in the pathogenesis of AR. Methods: Nasal tissues and peripheral blood mononuclear cells (PBMCs) were obtained from 17 patients with AR and 11 control subjects. Foxp3 was detected in nasal tissues by immunohistochemistry and real-time reverse transcription-polymerase chain reaction (RT-PCR). CD4+CD25+ T cells and Foxp3 were evaluated in PBMCs by using flow cytometry. Concentrations of interleukin-2 (IL-2) and interferon-, (IFN-,) were measured by enzyme-linked immunosorbent assay (ELISA) in cultured PBMCs in the presence or absence of stimulation with phorbol ester (PMA) and Ionomycin. Results: The numbers of Foxp3+ cells was 129.5 ± 35.6 and 44.2 ± 20.5 cells/mm2 in nasal mucosa of two groups (P < .05). There were less Foxp3+ lymphocytes and decreased Foxp3 mRNA in AR compared with the control (P < .05). The frequencies of the CD4+CD25+ population in PBMCs of two groups were 1.99 ± 0.95% and 3.55 ± 1.27% (P < .05). There was significant difference in the frequencies of the Foxp3+CD4+ CD25+ population (1.81 ± 0.77 vs 3.37 ± 1.04, P < .05) and mean fluorescence intensity (MFI) of Foxp3 (5.93 ± 2.64 vs 11.72 ± 4.29, P < .05) in PBMCs of two groups. After stimulation, the concentrations of IL-2 and IFN-, were 182.72 ± 85.11 pg/mL and 348.94 ± 151.88 pg/mL in PBMCs with AR, while those were 90.6 ± 61.5 pg/mL and 155.64 ± 68.33 pg/mL in controls (P < .05). Conclusion: Our results indicate that CD4+ CD25+ regulatory T cells as well as Foxp3 may play a crucial role in immunological imbalance of AR. These findings suggest that increasing Foxp3 and CD4+CD25+ T cells have the potential to be new therapeutic targets for the treatment of AR. [source] TLR3 modulates immunopathology during a Schistosoma mansoni egg-driven Th2 response in the lungEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2008Amrita D. Joshi Abstract We examined the role of TLR3 in Th2-driven pulmonary granulomatous disease, using wildtype (TLR3+/+) and TLR3 gene-deficient (TLR3,/,) mice in a well-established model of Schistosoma mansoni egg-induced pulmonary granuloma. The intravenous bolus injection of S. mansoni eggs into S. mansoni -sensitized TLR3+/+ mice was associated with an increase in TLR3 transcript expression in alveolar macrophages and ex vivo spleen and lung cultures at day 8 after egg injection. Lungs from TLR3,/, mice showed an increase in granuloma size, greater collagen deposition around the granuloma, and increased Th2 cytokine and chemokine levels compared with similarly sensitized and challenged TLR3+/+ mice. Macrophages from TLR3,/, mice exhibited an M2 phenotype characterized by increased arginase and CCL2 expression. Significantly greater numbers of CD4+CD25+ T cells were present in the lungs of TLR3,/, mice compared with TLR3+/+ mice at day 8 after egg embolization. Cells derived from granulomatous lung and lung draining lymph nodes of TLR3,/, mice released significantly higher levels of IL-17 levels relative to TLR3+/+ cells. Thus, our data suggest that TLR3 has a major regulatory role during a Th2-driven granulomatous response as its absence enhanced immunopathology. [source] IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2007Wanda Niedbala Abstract Epstein-Barr virus-induced gene,3 (EBI3) and the p35 subunit of IL-12 have been reported to form a heterodimeric hematopoietin in human and mouse. We have constructed a heterodimeric protein covalently linking EBI3 and p35, to form a novel cytokine which we now call IL-35. The Fc fusion protein of IL-35 induced proliferation of murine CD4+CD25+ and CD4+CD25, T cells when stimulated with immobilized anti-CD3 and anti-CD28 antibodies in vitro. The IL-35-expanded CD4+CD25+ T cell population expressed Foxp3 and produced elevated levels of IL-10, whereas the IL-35-induced CD4+CD25, T cells produced IFN-, but not IL-4. The in vitro expanded CD4+CD25+ T cells retained their suppressive functions against CD4+CD25, effector cells. Furthermore, when cultured with soluble anti-CD3 antibody and antigen-presenting cells, IL-35 suppressed the proliferation of CD4+CD25, effector cells. Moreover, IL-35 inhibited the differentiation of Th17 cells in vitro. In vivo, IL-35 effectively attenuated established collagen-induced arthritis in mice, with concomitant suppression of IL-17 production but enhanced IFN-, synthesis. Thus, IL-35 is a novel anti-inflammatory cytokine suppressing the immune response through the expansion of regulatory T cells and suppression of Th17 cell development. [source] Up-regulation of leukocyte CXCR4 expression by sulfatide: An L-selectin-dependent pathway on CD4+ T cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2007Pascal Duchesneau Abstract CXCR4 plays significant roles in immune and inflammatory responses and is important for selective recruitment of leukocytes. We previously showed that CXCR4 surface expression of human lymphocytes was affected by sulfatide, an in vivo ligand for L-selectin. Increased CXCR4 expression was shown to promote biologically relevant functions such as integrin-dependent adhesion and transmigration. Here, we show that sulfatide-induced CXCR4 up-regulation also occurs on other leukocyte subsets in humans and mice. B cells and CD4+CD25+ T cells had the highest CXCR4 up-regulation after sulfatide stimulation. Transfection of L-selectin was sufficient for K562 cells to acquire sulfatide-induced CXCR4 up-regulation, while analysis of L-selectin knockout mice revealed that this response was critically L-selectin dependent only for CD4+ T cells, suggesting an alternative pathway in CD8+ T cells and B cells. Sulfatide triggered several intracellular signaling events in CD4+ T cells, but only tyrosine kinase activation, including members of the Src family, were essential for L-selectin to CXCR4 signaling. CXCR4 up-regulation was rapid, enhanced CXCL12-induced signaling and increased chemotaxis toward CXCL12, and therefore has potentially important roles in vivo. Thus, the response to CXCL12 depends in part on tissue expression of sulfatide and, specifically in CD4+ T cells, also depends on the surface level of L-selectin. [source] Regulatory T cells and intestinal homeostasisIMMUNOLOGICAL REVIEWS, Issue 1 2005Janine L. Coombes Summary:, Murine models of inflammatory bowel disease (IBD) are useful tools for the study of the pathogenesis and regulation of intestinal inflammation. Colitis can be induced in immune-deficient mice following transfer of populations of T cells or following infection with Helicobacter hepaticus and other intestinal pathogens. In these situations, colitis occurs as a result of the absence of a specialized population of regulatory cells, as transfer of CD4+CD25+ T cells prevents disease. Importantly, from a clinical perspective, CD4+CD25+ T cells can also reverse an established colitis. CD4+CD25+ T cells proliferate both in the secondary lymphoid organs and at the site of inflammation, suggesting that regulation occurs both locally and systemically. CD4+CD25+ T cells are not only capable of regulating other T cells but are also capable of suppressing components of the innate immune system. Control of colitis is dependent on the presence of the immunosuppressive cytokines interleukin-10 and transforming growth factor-,, although their roles are divergent and complex. Regulatory T cells represent one of the host's mechanisms to prevent immune pathology during chronic immune stimulation. Enhancement of regulatory T-cell activity may be useful to control autoreactive T-cell responses and inhibit harmful inflammatory diseases such as asthma and IBD. [source] Regulatory T cells and autoimmune diseaseIMMUNOLOGICAL REVIEWS, Issue 1 2005Silke Paust Summary:, Although T-cell clones bearing T-cell receptors with high affinity for self-peptide major histocompatibility complex (MHC) products are generally eliminated in the thymus (recessive tolerance), the peripheral T-cell repertoire remains strongly biased toward self-peptide MHC complexes and includes autoreactive T cells. A search for peripheral T cells that might exert dominant inhibitory effects on autoreactivity has implicated a subpopulation of CD4+CD25+ T cells called regulatory T cells (Tregs). Here, we discuss the role of cytokines and costimulatory molecules in the generation, maintenance, and function of Tregs. We also summarize evidence for the involvement of Tregs in controlling autoimmune diseases, including type 1 diabetes, experimental autoimmune encephalomyelitis, and inflammatory bowel disease. Last, we discuss our recent definition of the potential role of B7 expressed on activated T-effector cells as a target molecule for Treg-dependent suppression. These observations suggest that the engagement of B7 on effector T cells transmits an inhibitory signal that blocks or attenuates effector T-cell function. We restrict our comments to the suppression mediated by cells within the CD4 lineage; the impact of the cells within the CD8 lineage that may suppress via engagement of Qa-1 on effector T cells is not addressed in this review. [source] Expression and functional characterization of FOXP3+CD4+ regulatory T cells in ulcerative colitis,INFLAMMATORY BOWEL DISEASES, Issue 2 2007Qi T. Yu BS Abstract Background: CD4+CD25+ regulatory T cells (TR) can prevent or treat experimental murine colitis but little is known about their potential role in human inflammatory bowel disease (IBD). FOXP3 is a transcription factor that plays a critical role in the development and function of CD4+CD25+ TR. The aim of this study was to examine the presence and functional characteristics of TR cells in colonic lymphoid tissues in patients with ulcerative colitis (UC). Methods: FOXP3 expression was assessed by flow cytometry, immunohistochemistry, and reverse-transcriptase polymerase chain reaction (RT-PCR). Functional characterization of CD4+CD25+ cells was analyzed by suppression of proliferation and secretion of cytokines by cocultured effector CD4+CD25, T cells. Results: FOXP3+CD4+ T cells are increased in the lamina propria (LP) of inflamed and noninflamed areas of UC colon compared to normal colon. CD4+CD25+ T cells in UC mesenteric lymph nodes (MLN) express FOXP3 mRNA and protein and suppress the proliferation of autologous MLN CD4+CD25, T cells. The suppressor activity of MLN CD4+CD25+ T cells is cell contact-dependent but cytokine-independent. In addition, CD4+CD25+ T cells potently suppress the production of both Th1 (IFN-,, IL-2) and Th2 (IL-5, IL-13) cytokines by cocultured CD4+CD25, T cells. FOXP3+ cells localized in the T-cell-rich areas of MLN and occasionally present in the follicles. Conclusions: There is an expansion of FOXP3+CD4+ T cells in mucosal lymphoid tissues in UC. CD4+CD25+ isolated from UC MLN express FOXP3 and display features of TR cells in spite of active mucosal inflammation. These data suggest that their suppressor activity may be abrogated in vivo or they are unable to counterbalance the chronic mucosal inflammation in UC. (Inflamm Bowel Dis 2007) [source] CD4+CD25+ cell depletion from the normal CD4+ T cell pool prevents tolerance toward the intestinal flora and leads to chronic colitis in immunodeficient miceINFLAMMATORY BOWEL DISEASES, Issue 6 2006Claudia Veltkamp MD Abstract Background: CD4+CD25+ regulatory T cells have been shown to prevent immune-mediated colitis in mice; however, it is unclear whether the absence of CD4+CD25+ in the normal CD4+ T cell pool is responsible for the development of chronic colitis. Using the T cell-deficient Tg,26 mouse model, we show that CD4+CD25, cells but not CD4+CD25+ cells induce a severe intestinal inflammation. Transfer of CD4+CD25+ cells, together with CD4+CD25, cells, ameliorated intestinal inflammation, and reconstitution with the whole mesenteric lymph node cell pool did not induce colitis in recipients. Transferred CD4+CD25, cells were found mainly in the mesenteric lymph nodes, where they showed an activated TH1-like phenotype. In the absence of regulatory CD4+CD25+ T cells, recipient CD4+ cells secreted IFN-, in response to stimulation with intestinal bacterial antigen that was prevented in vivo and in vitro by regulatory CD4+CD25+ cells. These studies suggest that CD4+CD25, cells have a strong colitogenic effect in the Tg,26 colitis model and that CD4+CD25+ cells may be the main regulators that prevent or downregulate the proinflammatory effect of colitogenic T cells in the Tg,26 mouse model. [source] A Possible Role of CD4+CD25+ T Cells as Well as Transcription Factor Foxp3 in the Dysregulation of Allergic RhinitisTHE LARYNGOSCOPE, Issue 5 2007Geng Xu MD Abstract Background: Allergic rhinitis (AR) is a Th2 predominant disease, and its pathogenic mechanism is still poorly understood. CD4+CD25+ T cells account for approximately 5% to 10% peripheral CD4+ T cells and has been shown to regulate the activation of effector T cells in the periphery. The activity of CD4+CD25+ T cells is associated with the transcription factor Foxp3. The present study aimed to evaluate the possible role of CD4+CD25+ T cells as well as Foxp3 in the pathogenesis of AR. Methods: Nasal tissues and peripheral blood mononuclear cells (PBMCs) were obtained from 17 patients with AR and 11 control subjects. Foxp3 was detected in nasal tissues by immunohistochemistry and real-time reverse transcription-polymerase chain reaction (RT-PCR). CD4+CD25+ T cells and Foxp3 were evaluated in PBMCs by using flow cytometry. Concentrations of interleukin-2 (IL-2) and interferon-, (IFN-,) were measured by enzyme-linked immunosorbent assay (ELISA) in cultured PBMCs in the presence or absence of stimulation with phorbol ester (PMA) and Ionomycin. Results: The numbers of Foxp3+ cells was 129.5 ± 35.6 and 44.2 ± 20.5 cells/mm2 in nasal mucosa of two groups (P < .05). There were less Foxp3+ lymphocytes and decreased Foxp3 mRNA in AR compared with the control (P < .05). The frequencies of the CD4+CD25+ population in PBMCs of two groups were 1.99 ± 0.95% and 3.55 ± 1.27% (P < .05). There was significant difference in the frequencies of the Foxp3+CD4+ CD25+ population (1.81 ± 0.77 vs 3.37 ± 1.04, P < .05) and mean fluorescence intensity (MFI) of Foxp3 (5.93 ± 2.64 vs 11.72 ± 4.29, P < .05) in PBMCs of two groups. After stimulation, the concentrations of IL-2 and IFN-, were 182.72 ± 85.11 pg/mL and 348.94 ± 151.88 pg/mL in PBMCs with AR, while those were 90.6 ± 61.5 pg/mL and 155.64 ± 68.33 pg/mL in controls (P < .05). Conclusion: Our results indicate that CD4+ CD25+ regulatory T cells as well as Foxp3 may play a crucial role in immunological imbalance of AR. These findings suggest that increasing Foxp3 and CD4+CD25+ T cells have the potential to be new therapeutic targets for the treatment of AR. [source] Differential Role of Naïve and Memory CD4+ T-Cell Subsets in Primary AlloresponsesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010D. Golshayan The T cell response to major histocompatibility complex (MHC) alloantigens occurs via two main pathways. The direct pathway involves the recognition of intact allogeneic MHC:peptide complexes on donor cells and provokes uniquely high frequencies of responsive T cells. The indirect response results from alloantigens being processed like any other protein antigen and presented as peptide by autologous antigen-presenting cells. The frequencies of T cells with indirect allospecificity are orders of magnitude lower and comparable to other peptide-specific responses. In this study, we explored the contributions of naïve and memory CD4+ T cells to these two pathways. Using an adoptive transfer and skin transplantation model we found that naive and memory CD4+ T cells, both naturally occurring and induced by sensitization with multiple third-party alloantigens, contributed equally to graft rejection when only the direct pathway was operative. In contrast, the indirect response was predominantly mediated by the naïve subset. Elimination of regulatory CD4+CD25+ T cells enabled memory cells to reject grafts through the indirect pathway, but at a much slower tempo than for naïve cells. These findings have implications for better targeting of immunosuppression to inhibit immediate and later forms of alloimmunity. [source] Everolimus and Basiliximab Permit Suppression by Human CD4+CD25+ Cells in vitroAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2005David S. Game Immunosuppressive drugs are essential for the prevention of acute transplant rejection but some may not promote long-term tolerance. Tolerance is dependent on the presence and regulatory function of CD4+CD25+ T cells in a number of animal models. The direct effects of immunosuppressive drugs on CD4+CD25+ cells, particularly those that interfere with IL-2 signaling are uncertain. We studied the effects of the rapamycin derivative everolimus and the anti-CD25 monoclonal antibody basiliximab on the regulatory capacity of human CD4+CD25+ cells in vitro. Both drugs permitted the suppression of proliferation and IFN-, secretion by CD4+CD25, cells responding to allogeneic and other polyclonal stimuli; CTLA-4 expression was abolished on CD4+CD25+ cells without compromising their suppressive ability. Everolimus reduced IFN-, secretion by CD4+CD25, cells before the anti-proliferative effect: this is a novel finding. Exogenous IL-2 and IL-15 could prevent the suppression of proliferation by CD4+CD25+ cells and the drugs could not restore suppression. By contrast, suppression of IFN-, secretion was only slightly impeded with the exogenous cytokines. Finally, CD4+CD25+ cells were more resistant than CD4+CD25, cells to the pro-apoptotic action of the drugs. Together these data suggest that CD4+CD25+ cells may still exert their effects in transplant patients taking immunosuppression that interferes with IL-2 signaling. [source] CD4+CD25+ regulatory T cells: I. Phenotype and physiologyAPMIS, Issue 10 2004Review article The immune system protects us against foreign pathogens. However, if fine discrimination between self and non-self is not carried out properly, immunological attacks against self may be launched leading to autoimmune diseases, estimated to afflict up to 5% of the population. During the last decade it has become increasingly clear that regulatory CD4+CD25+ T cells (Treg cells) play an important role in the maintenance of immunological self-tolerance, and that this cell subset exerts its function by suppressing the proliferation or function of autoreactive T cells. Based on human and murine observations, this review presents a characterization of the phenotype and functions of the Treg cells in vitro and in vivo. An overview of the surface molecules associated with and the cytokines produced by the Treg cells is given and the origin, activation requirements and mode of action of the Treg cells are discussed. Finally, we address the possibility that Treg cells may play a central role in immune homeostasis, regulating not only autoimmune responses, but also immune responses toward foreign antigens. [source] CD4+CD25+ regulatory T cells: II.APMIS, Issue 10 2004Origin, clinical aspects, disease models Autoimmune diseases afflict approximately 5% of the population and reflect a failure in the immune system to discriminate between self and non-self resulting in the breakdown of self-tolerance. Regulatory CD4+CD25+ T cells (Treg cells) have been shown to play an important role in the maintenance of immune homeostasis and self-tolerance by counteracting the development and effector functions of potentially autoreactive T cells. We have in the previous APMIS review described the phenotype and physiology of Treg cells. The present overview deals with the thymic origin of Treg cells and their role in disease models such as autoimmune gastritis and inflammatory bowel disease. Finally, we will consider some aspects of the therapeutic potential of Treg cells. [source] Increased bone density and resistance to ovariectomy-induced bone loss in FoxP3-transgenic mice based on impaired osteoclast differentiationARTHRITIS & RHEUMATISM, Issue 8 2010Mario M. Zaiss Objective Immune activation triggers bone loss. Activated T cells are the cellular link between immune activation and bone destruction. The aim of this study was to determine whether immune regulatory mechanisms, such as naturally occurring Treg cells, also extend their protective effects to bone homeostasis in vivo. Methods Bone parameters in FoxP3-transgenic (Tg) mice were compared with those in their wild-type (WT) littermate controls. Ovariectomy was performed in FoxP3-Tg mice as a model of postmenopausal osteoporosis, and the bone parameters were analyzed. The bones of RAG-1,/, mice were analyzed following the adoptive transfer of isolated CD4+CD25+ T cells. CD4+CD25+ T cells and CD4+ T cells isolated from FoxP3-Tg mice and WT mice were cocultured with monocytes to determine their ability to suppress osteoclastogenesis in vitro. Results FoxP3-Tg mice developed higher bone mass and were protected from ovariectomy-induced bone loss. The increase in bone mass was found to be the result of impaired osteoclast differentiation and bone resorption in vivo. Bone formation was not affected. Adoptive transfer of CD4+CD25+ T cells into T cell,deficient RAG-1,/, mice also increased the bone mass, indicating that Treg cells directly affect bone homeostasis without the need to engage other T cell lineages. Conclusion These data demonstrate that Treg cells can control bone resorption in vivo and can preserve bone mass during physiologic and pathologic bone remodeling. [source] Lower expression levels of the programmed death 1 receptor on CD4+CD25+ T cells and correlation with the PD-1.3A genotype in patients with systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 6 2010Helga Kristjansdottir Objective A genetic polymorphism in the programmed death 1 (PD-1) gene encoding the coinhibitory PD-1 immunoreceptor, PD-1.3A, is associated with systemic lupus erythematosus (SLE). The aim of this study was to assess PD-1 receptor expression in patients with SLE, in comparison with relatives and unrelated healthy controls, and to identify correlations of lower expression levels of PD-1 receptor with the PD-1.3A genotype. Methods Patients with SLE, patients' relatives, and unrelated healthy control subjects from Iceland and Sweden were studied. Peripheral blood mononuclear cells (PBMCs) were stimulated with anti-CD3/anti-CD28, and PD-1 expression was analyzed by flow cytometry. PD-1.3A/G genotyping was performed using polymerase chain reaction,restriction fragment length polymorphism analysis. Results PD-1 expression on PBMCs was induced after antibody stimulation, showing increases of 2.1-fold in SLE patients, 3.1-fold in relatives, and 5.1-fold in healthy controls. The frequency of PD-1+ cells was significantly lower in SLE patients compared with relatives and healthy controls. PD-1 expression on PD-1+ cells and on CD4+CD25+ T cells was significantly lower in SLE patients and relatives compared with healthy controls. PD-1 expression was significantly elevated on CD25high cells. Levels of PD-1 expression on CD25high and CD25intermediate cells were significantly lower in SLE patients compared with healthy controls. PD-1 was expressed on both FoxP3, and FoxP3+ cells. Lower expression of PD-1 was significantly correlated with the PD-1.3A/G genotype. Conclusion The results demonstrate significantly lower PD-1 receptor expression in SLE patients and their relatives and reveal a significant correlation of lower PD-1 expression with the PD-1.3A allele. Thus, PD-1.3A may contribute to abnormalities in PD-1 receptor expression on CD4+CD25+ T cells in patients with SLE, providing support for an important role of the PD-1 pathway in SLE and, possibly, in other autoimmune diseases. [source] Sequential Involvement of Two Distinct CD4+ Regulatory T Cells during the Course of Transplantable Tumor Growth and Protection from 3,Methylcholanthrene-induced Tumorigenesis by CD25,depletionCANCER SCIENCE, Issue 8 2002Isao Tawara The involvement of two phenotypically different regulatory T cells in different stages of tumor growth was investigated. Treatment of BALB/c mice with anti-CD25 monoclonal antibody (mAb) (PC61), but not anti-CD4 mAb (GK1.5) before RL male 1 or Meth A inoculation caused tumor rejection. On the other hand, treatment of BALB/c mice with anti-CD4 mAb (GK1.5) but not anti-CD25 mAb (PC61) on day 6 after inoculation of the same tumors caused rejection. The findings suggest that CD4+CD25+ T cells downregulated the rejection response in the early stage of tumor growth. On the other hand, putative CD4+CD25, T cells downregulated the tumor rejection response in the late stage. Both CD4+CD25+ and putative CD4+CD25-T cells appeared to inhibit the efficient generation of cytotoxic T lymphocytes (CTL). The present study also demonstrated that the treatment of BALB/c mice with anti-CD25 mAb (PC61) at 4 or 6 weeks after 3,methylcholanthrene (3,MC) inoculation retarded tumor occurrence and prolonged survival. [source] The immune system in healthy adults and patients with atopic dermatitis seems to be affected differently by a probiotic interventionCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2008A. Roessler (nee Klein) Summary Background Probiotic bacteria are proposed to alleviate atopic dermatitis (AD) in infants. There are few indications about the effect of probiotics on AD in adults. Objective The purpose of this study was to elucidate the influence of a probiotic drink containing a combination of the probiotics Lactobacillus paracasei Lpc-37, Lactobacillus acidophilus 74-2 and Bifidobacterium animalis subsp. lactis DGCC 420 (B. lactis 420) in healthy volunteers and in patients with AD on clinical and immunological parameters and their detection in feces. Methods A double-blind, placebo-controlled, randomized cross-over study was conducted in 15 healthy adults and 15 patients with AD. The probiotic product or placebo was given over 8 weeks. A 2-week washout period was interconnected before the intervention was crossed. At the end of each period, blood and stool samples were collected. In patients, the severity of AD was evaluated using the Scoring of Atopic Dermatitis (SCORAD). Results L. paracasei and B. lactis were recovered in high numbers in feces after supplementation, whereas L. acidophilus marginally increased. In patients, the SCORAD tended to decrease by 15.5% (P=0.081). Major lymphocyte subsets were not affected by the probiotic intervention. However, CD57+ increased significantly (P=0.034) in healthy subjects after probiotic intake and was not changed in patients, whereas CD4+CD54+ decreased significantly (P=0.031) in patients with AD and remained uninfluenced in healthy subjects. The expression of CD4+CD25+ T cells was similar in healthy subjects and AD patients. The phagocytic activity of monocytes and granulocytes was significantly increased in healthy subjects after probiotic intervention (P=0.014). Conclusion L. paracasei Lpc-37 and B. lactis 420 are able to colonize the intestine transiently. This study reveals that the probiotics differently modulate peripheral immune parameters in healthy subjects and patients with AD. [source] The role of CD4+CD25+ T cells in autoantibody production in murine lupusCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2006W.-T. Hsu Summary Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease characterized by the loss of tolerance to self-antigen. Because it is currently not known if regulatory T (Treg) cells are involved in the pathogenesis, we determined the frequency of CD4+CD25+ T cells and assayed the related gene expression levels in CD4+CD25+ T cells isolated from both lupus mice (NZB/NZW F1) and normal control mice (DBA2/NZW F1). The results showed that the frequency of CD4+CD25+ T cells in lupus mice was lower than that of normal mice. Except for the high expression level of interleukin (IL)-10 mRNA, CD4+CD25+ T cells from lupus mice expressed normal forkhead box P3 (Foxp3) and transforming growth factor (TGF)-, mRNA, and exerted suppressive functions. Furthermore, we depleted CD25+ Treg cells of non-autoimmune mice with anti-CD25 antibody and broke their tolerance with apoptotic cell-pulsed dendritic cells for the follow-up of autoantibody levels. The mice in the CD25+ cell-depleted group had higher titres of anti-double-strand/single-strand DNA antibodies than those of the isotype control antibody-treated group. These findings indicated that CD4+CD25+ T cells might be involved in the regulatory mechanism of autoantibody production. [source] | ||||||||||