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Helper T Cells (helper t + cell)
Selected AbstractsCellular dynamics in the draining lymph nodes during sensitization and elicitation phases of contact hypersensitivityCONTACT DERMATITIS, Issue 5 2007Jeppe Madura Larsen Background:, The different role of various immunological effector cells in contact hypersensitivity (CHS) is receiving increased attention. During the past decade, the involvement of different cell types in CHS has been investigated by the use of antibody-induced depletion of specific subtypes of immunological cells and by studying knockout mice lacking one or more of these immunological cell populations. Objectives:, To develop a method for studying the collective cellular dynamics of immune cells in the draining lymph nodes during CHS in intact animals. Patients/Methods:, Mice were sensitized and/or challenged with 2,4-dinitrofluorobenzene or oxazolone. Using multi-parameter flow cytometry we determined the proliferation, activation state, and absolute number of helper T cells, cytotoxic T cells, B cells, and natural killer cells in the draining lymph nodes. Results:, The presented method can be applied to evaluate the effect of different contact allergens on various cell populations of the immune system. Conclusions:, Our study support recent findings that several cell types seem to be involved in CHS. [source] Cross-Primed CD8+ Cytotoxic T cells Induce Severe Helicobacter -associated Gastritis in the Absence of CD4+ T cellsHELICOBACTER, Issue 5 2007Toshiro Fukui Abstract Background:, Although previous studies have reported important roles of CD4+ type1-helper T cells and regulatory T cells in Helicobacter -associated gastritis, the significance of CD8+ cytotoxic T cells remains unknown. To study the roles of CD8+ T cells, we examined the immune response in the gastric mucosa of Helicobacter felis -infected major histocompatibility complex (MHC) class II-deficient (II,/,) mice, which lack CD4+ T cells. Materials and methods:, Stomachs from H. felis -infected wild-type and infected MHC II,/, mice were examined histologically and immunohistochemically. Gastric acidity and serum levels of anti- H. felis antibodies were measured. The expression of pro-inflammatory and anti-inflammatory cytokine, Fas-ligand, perforin, and Foxp3 genes in the gastric mucosa was investigated. Results:,H. felis -infected MHC II,/, mice developed severe gastritis, accompanied by marked infiltration of CD8+ cells. At 1 and 2 months after inoculation, mucosal inflammation and atrophy were more severe in MHC II,/, mice, although gastritis had reached similar advanced stages at 3 months after inoculation. There was little infiltration of CD4+ cells, and no Foxp3 -positive cells were detected in the gastric mucosa of the infected MHC II,/, mice. The expression of the interleukin-1, and Fas-ligand genes was up regulated, but that of Foxp3 was down regulated in the infected MHC II,/, mice. Serum levels of anti- H. felis antibodies were lower in the infected MHC II,/, mice, despite severe gastritis. Conclusions:, The present study suggests that cross-primed CD8+ cytotoxic T cells can induce severe H. -associated gastritis in the absence of CD4+ helper T cells and that Foxp3 -positive cells may have an important role in the control of gastric inflammation. [source] Multi-tasking of helper T cellsIMMUNOLOGY, Issue 2 2010Yisong Y. Wan Summary CD4 T helper cells (Th) are critical in combating pathogens and maintaining immune homeostasis. Since the establishment of the Th1,Th2 paradigm in the 1980s, many types of specialized Th cells, including Th1, Th2, Th17, Th9, follicular helper T and regulatory T, have been identified. We have become accustomed to the idea that different Th cells are ,committed' to their paths but recent emerging evidence suggests that under certain conditions, seemingly committed Th cells possess plasticity and may convert into other types of effector cells. In this review, we will first introduce the major sub-types of Th cells that are involved in immune regulation. Then, we will describe in detail the inter-convertibility of Th cells among different sub-types under in vitro and in vivo conditions. Finally, we will discuss our current understanding of the underlying mechanisms on how a particular type of Th cells may convert into other types of Th cells. [source] Amelioration of doxorubicin-induced myocardial oxidative stress and immunosuppression by grape seed proanthocyanidins in tumour-bearing miceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2005Xiao-Yu Zhang We have investigated the protective effects of grape seed proanthocyanidins on doxorubicin-induced toxicity in tumour-bearing mice. The intraperitoneal administration of doxorubicin (2 mg kg,1 every other day, cumulative dosage for 18 mg kg,1) significantly inhibited the growth of sarcoma 180, and induced myocardial oxidative stress with decreased superoxide dismutase and glutathione peroxidase activity while increasing malondialdehyde formation in the heart or serum. Doxorubicin-induced myocardial oxidative stress also reduced lactate dehydrogenase and creatine kinase activity in the heart and elevated their levels in the serum. Doxorubicin also affected immune functions of tumour-bearing mice with significantly decreased interleukin-2 (IL-2) and interferon-, (INF-,) production, and slightly decreased natural killer (NK) cell cytotoxicity, lymphocyte proliferation and CD4+/CD8+ ratio. It markedly increased the percentages of cytotoxic T cells (CD3+CD8+), helper T cells (CD3+CD4+), IL-2R+CD4+, and IL-2R+ cells as compared with untreated tumour-bearing mice. The intragastric administration of proanthocyanidin (200 mg kg,1 daily) significantly inhibited tumour growth, and increased NK cell cytotoxicity, lymphocyte proliferation, CD4+/CD8+ ratio, IL-2 and INF-, production. Moreover, proanthocyanidin strongly enhanced the anti-tumour effect of doxorubicin and the above immune responses, and completely eliminated myocardial oxidative stress induced by doxorubicin. In conclusion, intragastric administration of proanthocyanidin could enhance the anti-tumour activity of doxorubicin and ameliorate doxorubicin-induced myocardial oxidative stress and immunosuppression in tumour-bearing mice. [source] Cutaneous T-cell lymphomaJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2 2003EA Kotz ABSTRACT Cutaneous T-cell lymphoma (CTCL) is a neoplasm of helper T cells whose first manifestations usually appear in the skin. The various forms of CTCL are distinguished by both clinical features and histopathology. Early on, the diagnosis may be difficult to establish because of its numerous, and often non-specific, clinical presentations. Further, the pathological findings of early lesions may lack the diagnostic features observed in well-developed or advanced disease. The diagnosis of CTCL must be considered in any patient with a chronic, therapy-resistant condition of the skin. In patients with non-specific histological findings, a high index of suspicion and multiple biopsies may eventually lead to a diagnosis of CTCL. Once the diagnosis of CTCL is established, accurate staging is essential both for its effect on treatment decisions and for its prognostic value. In general, CTCL is a chronic, slowly progressive disease with a long evolution. The development of tumours is a poor prognostic sign, as is erythroderma. The Sezary syndrome is a distinct form of erythrodermic CTCL that is characterized by exfoliative erythroderma, lymphadenopathy, lymphocytosis, intense pruritus, and circulating large, abnormal lymphocytes (Sezary cells). When death does occur, it is most often due to septicemia. Treatment of CTCL must be tailored to the individual patient. The most commonly employed treatment options are photochemotherapy and topical chemotherapy. [source] Binding interactions between peptides and proteins of the class II Major Histocompatibility ComplexMEDICINAL RESEARCH REVIEWS, Issue 2 2002Benjamin J. McFarland Abstract The activation of helper T cells by peptides bound to proteins of the class II Major Histocompatibility Complex (MHC II) is pivotal to the initiation of an immune response. The primary functional requirement imposed on MHC II proteins is the ability to efficiently bind thousands of different peptides. Structurally, this is reflected in a unique architecture of binding interactions. The peptide is bound in an extended conformation within a groove on the membrane distal surface of the protein that is lined with several pockets that can accommodate peptide side-chains. Conserved MHC II protein residues also form hydrogen bonds along the length of the peptide main-chain. Here we review recent advances in the study of peptide-MHC II protein reactions that have led to an enhanced understanding of binding energetics. These results demonstrate that peptide-MHC II protein complexes achieve high affinity binding from the array of hydrogen bonds that are energetically segregated from the pocket interactions, which can then add to an intrinsic hydrogen bond-mediated affinity. Thus, MHC II proteins are unlike antibodies, which utilize cooperativity among binding interactions to achieve high affinity and specificity. The significance of these observations is discussed within the context of possible mechanisms for the HLA-DM protein that regulates peptide presentation in vivo and the design of non-peptide molecules that can bind MHC II proteins and act as vaccines or immune modulators. © 2002 John Wiley & Sons, Inc. Med Res Rev, 22, No. 2, 168,203, 2002; DOI 10.1002/med.10006 [source] A new standard for the assessment of disease progression in murine cutaneous leishmaniasisPARASITE IMMUNOLOGY, Issue 5 2000Lynden J.roberts Infection of mice with Leishmania major has been used both as a model for the cutaneous disease in humans and as a model for the more general control and function of helper T cells in immunity. In both cases, disease patterns and disease progression have been assessed by two complementary methods, lesion size and parasite burden in the draining lymph nodes. We propose a much improved method for the graphical representation of lesion development which conveys more information with better accuracy. We also describe a polymerase chain reaction method for determining parasite burden, which is faster and allows the analysis of larger numbers of experimental animals than the current limiting dilution analysis. Moreover, these methods are equally applicable to other infectious diseases, an obvious one being schistosomiasis. [source] Accumulation of IL-17-Positive Cells in Decidua of Inevitable Abortion CasesAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010Akitoshi Nakashima Citation Nakashima A, Ito M, Shima T, Bac ND, Hidaka T, Saito S. Accumulation of IL-17-positive cells in decidua of inevitable abortion cases. Am J Reprod Immunol 2010 Problem, Th17 cells, a new subset of helper T cells, have been focused on as a producer pro-inflammatory cytokines. It is, however, still unknown how Th17 cells affect pregnancy outcome. We investigated the expression of IL-17-producing cells in human spontaneous abortion. Method of study, IL-17 expression was analyzed in decidual tissues among normal pregnancy, missed abortion, and inevitable abortion cases by immunohistochemistry and flow cytometry. Results, IL-17+ cells were accumulated in decidua and were detected in decidual CD4+ T cells and few decidual CD8+ T cells in spontaneous abortion cases. The number of decidual IL-17+ cells in inevitable abortion cases involving active genital bleeding was significantly higher than that in normal pregnancy cases (P < 0.05). On the other hand, there were no significant differences in the numbers of decidual IL-17+ cells between missed abortion cases and normal pregnancy subjects. Furthermore, the number of IL-17+ cells was positively correlated with the number of neutrophils in spontaneous abortion cases. Conclusion, IL-17+ cells might be involved in the induction of inflammation in the late stage of abortion, but not in the early stage of abortion. [source] Emerging from the shadows: Follicular helper T cells in autoimmunityARTHRITIS & RHEUMATISM, Issue 1 2010Leah D. DiPlacido No abstract is available for this article. [source] Expansion of circulating T cells resembling follicular helper T cells is a fixed phenotype that identifies a subset of severe systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 1 2010Nicholas Simpson Objective In the sanroque mouse model of lupus, pathologic germinal centers (GCs) arise due to increased numbers of follicular helper T (Tfh) cells, resulting in high-affinity anti,double-stranded DNA antibodies that cause end-organ inflammation, such as glomerulonephritis. The purpose of this study was to examine the hypothesis that this pathway could account for a subset of patients with systemic lupus erythematosus (SLE). Methods An expansion of Tfh cells is a causal, and therefore consistent, component of the sanroque mouse phenotype. We validated the enumeration of circulating T cells resembling Tfh cells as a biomarker of this expansion in sanroque mice, and we performed a comprehensive comparison of the surface phenotype of circulating and tonsillar Tfh cells in humans. This circulating biomarker was enumerated in SLE patients (n = 46), Sjögren's syndrome patients (n = 17), and healthy controls (n = 48) and was correlated with disease activity and end-organ involvement. Results In sanroque mice, circulating Tfh cells increased in proportion to their GC counterparts, making circulating Tfh cells a feasible human biomarker of this novel mechanism of breakdown in GC tolerance. In a subset of SLE patients (14 of 46), but in none of the controls, the levels of circulating Tfh cells (defined as circulating CXCR5+CD4+ cells with high expression of Tfh-associated molecules, such as inducible T cell costimulator or programmed death 1) were increased. This cellular phenotype did not vary with time, disease activity, or treatment, but it did correlate with the diversity and titers of autoantibodies and with the severity of end-organ involvement. Conclusion These findings in SLE patients are consistent with the autoimmune mechanism in sanroque mice and identify Tfh effector molecules as possible therapeutic targets in a recognizable subset of patients with SLE. [source] Plasma-soluble Fas (APO-1, CD95) and soluble Fas ligand in immune thrombocytopenic purpuraEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2000Chie Yoshimura Abstract: We investigated the levels of various cytokines and soluble factors in ITP patients, in order to determine the influence of these factors on the pathogenesis of ITP. We found increases in IL-2, IL-6, IFN-,, and M-CSF levels in ITP patients compared with those in healthy individuals. On lymphocyte phenotype analysis, we found no clear difference in total T cell population (CD2+ CD19, cells) or cytotoxic T cell frequency (CD8+ CD11b, cells) between these two groups. The frequency of helper/inducer T cells (CD4+ CD8, cells) was decreased in ITP patients. There was a significant increase in activated T cells (CD3+ HLA-DR+ cells) in ITP patients. Furthermore, frequencies of NK cells of potent activity (CD16+ CD56+ cells) were significantly elevated in ITP patients. Seventeen of the 54 ITP patients (31.5%) had elevated levels of sFas, and 11 of the 54 patients (20.4%) of sFasL. In addition, a significant increase of sFasL was observed in sFas-positive ITP patients, and in these patients the sFasL level was correlated with that of sFas (r=0.687, p<0.01). We found significant increases in IL-2 and sIL-2R levels in sFas-positive ITP patients. For other factors examined, however, there were no differences in level between sFas-positive and-negative ITP patients. Percentages of activated T cells (CD3+ and HLA-DR+ cells) and NK cells (CD16+ and CD56+ cells) were significantly higher in sFas-positive ITP patients than in sFas-negative ITP patients. These findings suggests that the pathogenesis of ITP includes alteration of the Fas/FasL pathway. [source] | ||||||||||||||||||||||