Home About us Contact
|
Home About us Contact | ||
|
|
||
Antigen Stimulation (antigen + stimulation)
Selected AbstractsT-cell tolerance induced by repeated antigen stimulation: Selective loss of Foxp3, conventional CD4 T cells and induction of CD4 T-cell anergyEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2009Lena Eroukhmanoff Abstract Repeated immunization of mice with bacterial superantigens induces extensive deletion and anergy of reactive CD4 T cells. Here we report that the in vitro proliferation anergy of CD4 T cells from TCR transgenic mice immunized three times with staphylococcal enterotoxin B (SEB) (3× SEB) is partially due to an increased frequency of Foxp3+ CD4 T cells. Importantly, reduced number of conventional CD25, Foxp3, cells, rather than conversion of such cells to Foxp3+ cells, was the cause of that increase and was also seen in mice repeatedly immunized with OVA (3× OVA) and OVA,peptide (OVAp) (3× OVAp). Cell-transfer experiments revealed profound but transient anergy of CD4 T cells isolated from 3× OVAp and 3× SEB mice. However, the in vivo anergy was CD4 T-cell autonomous and independent of Foxp3+ Treg. Finally, proliferation of transferred CD4 T cells was inhibited in repeatedly immunized mice but inhibition was lost when transfer was delayed, despite the maintenance of elevated frequency of Foxp3+ cells. These data provide important implications for Foxp3+ cell-mediated tolerance in situations of repeated antigen exposure such as human persistent infections. [source] Multispecific responses by T cells expanded by endogenous self-peptide/MHC complexesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2007Guifang Cai Abstract The paradox of autoreactivity to self-peptides in physiological as opposed to pathological immune responses is not well understood. Here, we directly examined the human T cell response to endogenous self-peptides in a series of healthy subjects. CFSE-labeled T cells were stimulated with unmanipulated antigen-presenting cells containing endogenous self-antigen, and the resulting CD4+ populations entering into cell cycle (CFSElow) or non-proliferating CD4+ cells (CFSEhigh) were single-cell sorted, cloned and screened against a panel of self-antigens and microbial recall antigens to interrogate their antigen reactivity. The percentage of CD4+ T cells entering cell cycle in response to self-peptide/MHC was calculated to be 0.04%, and entry into cell cycle was dependent upon CD28 costimulation. Clones derived from CFSElow T cells exhibited significantly greater cross-reactivity to multiple antigens than CFSEhigh clones or other CD4+ clones generated after microbial antigen stimulation. Sequencing the TCR, chains indicated that CFSElow clones were indeed clonal. These data demonstrate that T cell clones generated on stimulation by endogenous self-peptides exhibit a high degree of multispecificity, and we speculate that their multispecificity is based upon recognition of shared-backbone MHC determinants. [source] Inverse correlation between IL-7 receptor expression and CD8 T cell exhaustion during persistent antigen stimulationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2005Abstract Persistence is a hallmark of infection by viruses such as HIV, hepatitis B virus, hepatitis C virus and LCMV. In the case of LCMV, persistence may often be associated with exhaustion of CD8+ T cells. We demonstrate here that persistent antigen suppressed IL-7R, expression and this correlated with T cell exhaustion and reduced expression of the anti-apoptotic molecule B cell leukemia/lymphoma 2 (Bcl-2). In contrast, exposure to short-lived antigen only temporarily suppressed IL-7R, expression, failed to induce T cell exhaustion, and primed T cells. Persistent antigen also suppressed IL-7R, expression on primed T cells and this correlated with exhaustion of a previously stable primed T cell population. These findings suggest that antigen longevity regulates T cell fate. [source] Circulating T-Cell Response to Helicobacter pylori Infection in Chronic GastritisHELICOBACTER, Issue 3 2000Zhigang Ren Background.Helicobacter pylori elicits a specific humoral and cellular immune response. There is increasing evidence that the type of T-cell response contributes to clinical outcome in H. pylori infection. Materials and Methods. The host response to H. pylori infection in 34 subjects with chronic gastritis was examined in terms of T-cell proliferation and cytokine production in whole-blood cultures stimulated or unstimulated with H. pylori acid-glycine extract antigens (AGE). Results. The proliferative response in whole-blood cultures was similar for both H. pylori,positive and ,negative subjects stimulated with H. pylori AGE. While an increase in interferon-, (IFN-,) production was observed from both H. pylori,positive and ,negative subjects with gastritis, significantly higher levels of IFN-, were detected in the former when stimulated with H. pylori AGE. In contrast, interleukin 4 (IL-4) was undetectable regardless of antigen stimulation. However, if an in situ IL-4 antibody capture assay was used, antigen-independent production of IL-4 was detected, but there was no difference between H. pylori,positive and ,negative subjects with gastritis. After eradication of H. pylori, antigen-induced production of IL-4 was increased, with no decrease in the levels of secretion of IFN-,. IL-4 production was dependent on CD4+ T cells, as addition of anti-CD4 but not anti-CD8 mouse monoclonal antibody or matched IgG isotype to the whole-blood culture inhibited the production of IL-4. Conclusion. The results suggest that a shift toward a balanced Th1-Th2 response due to an increase in antigen-induced IL-4 production from CD4+ T cells follows eradication. We suggest that the downregulation of mucosal inflammation consequent on reduction in antigen levels or removal of downregulation after eradication of H. pylori contributes to this shift in cytokine balance. [source] Modulation of immune response with cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin-induced anergic T cells in chronic idiopathic thrombocytopenic purpura,JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2008X.-L. ZHANG Summary.,Background:,Platelet glycoprotein (GP)-reactive CD4+ T cells are essential for the stimulation and maintenance of antiplatelet autoantibody production in chronic idiopathic thrombocytopenic purpura (ITP). Blocking costimulatory signals could result in platelet-specific T-cell anergy. Methods:,GP-specific CD4+ T cells from patients with ITP were made anergic using cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin (CTLA4-Ig). The CTLA4-Ig-induced GP-specific anergic T cells were investigated for their inhibitory function on GP-reactive T-cell proliferation and antibody production with in vitro culture systems. To further analyze their tolerizing mechanisms, we cocultured GP-anergic T cells with dendritic cells (DCs) from patients with ITP. Results:,Our studies demonstrated that the anergized GP-specific T cells have profound effects on both GP-specific T-cell proliferation and antibody production. These anergic T cells exerted their suppressive effects mainly in a cell contact-dependent manner, and they were not constitutively suppressive but required specific antigen stimulation to make DCs tolerogenic. The anergic T-cell-modulated DCs could induce the autoreactive T cells to be tolerant, and this effect was not restricted to T cells of the same specificity. Conclusion:,Our studies demonstrate the efficacy of CTLA4-Ig in suppressing the pathologic autoimmune responses in ITP. These findings provide new insights into the underlying mechanisms of anergy induction in chronic ITP. [source] Release of prostaglandin D2 and leukotriene C4 in response to hyperosmolar stimulation of mast cellsALLERGY, Issue 12 2006M. Gulliksson Background:, Mannitol-induced bronchoconstriction in subjects with exercise-induced asthma is associated with increased urinary excretion of 9,, 11, -PGF2, a metabolite of prostaglandin D2 (PGD2) serving as a mast cell marker. It has however been questioned whether or not human mast cells release PGD2 and leukotriene C4 (LTC4) after osmotic challenge with mannitol in vitro. Methods:, Cord blood-derived human mast cells were stimulated osmotically, immunologically or with a combination of both. Supernatants were analysed for PGD2, LTC4 and histamine contents with enzyme immunoassays. Results:, Significant release of de novo synthesized eicosanoids, predominantly PGD2 [12 (8.8, 14) pmol/106cells; median (25th, 75th percentile) but also LTC4 (0.1 (0.08, 0.15) pmol/106 cells] were found in mast cells in vitro in response to 0.7 M mannitol stimulation. A massive release of histamine [70 (5.3)% of total; mean (SEM)] was also found. There were no correlations between the levels of released mediators after mannitol stimulation. In contrast, there was a correlation between release of PGD2 and LTC4, following immunological stimulation. Conclusion:, The findings support that hyperosmolar challenge activates mast cells, but different than antigen stimulation. [source] Ocular adnexal lymphoma and Helicobacter pylori gastric infection,AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2010Didier Decaudin There is a causal association between Helicobacter pylori (Hp) gastric infection and the development of gastric MALT lymphoma. In contrast, the link between Hp gastric infection and the development of extragastric lymphoma has not been thoroughly investigated. We, therefore, studied the prevalence of gastric Hp infection at initial diagnosis of ophthalmologic and nonophthalmologic extragastric lymphoma patients. Three cohorts of patients were studied: a first one of 83 patients with OAL, a second one of 101 patients with extraophthalmologic extragastric lymphoma, and a third one of 156 control individuals (control) without malignant lymphoma. Gastric Hp infection was investigated by histopathological analysis and Hp -specific PCR assay on gastric biopsy tissue samples. We found gastric Hp infection in 37 OAL patients (45%), in 25 extraophthalmologic extragastric lymphoma cases (25%), and in 18 controls individuals (12%) (P < 0.0001 OAL/C and P < 0.01 OAL/extra-OAL cases). Gastritis was found in 51% and 9% of Hp -positive and Hp -negative lymphoma patients, respectively (P < 10,4). Gastric Hp infection only correlated with MALT/LPL lymphoma (P = 0.03). There is a significant association between gastric Hp infection and MALT/LPL OAL. This suggests a novel mechanism of indirect infection-associated lymphomagenesis whereby chronic local antigen stimulation would lead to the emergence of ectopic B-cell lymphoma. © 2010 Wiley-Liss, Inc. Am. J. Hematol. [source] Synovial lymphocyte responses to microbiologic antigen stimulation indicate the etiology of undifferentiated and reactive arthritis, and possibly of rheumatoid arthritis: Comment on the article by Schnarr et alARTHRITIS & RHEUMATISM, Issue 8 2002Denys K. Ford MD No abstract is available for this article. [source] IgV gene intraclonal diversification and clonal evolution in B-cell chronic lymphocytic leukaemiaBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2006Davide Bagnara Summary Intraclonal diversification of immunoglobulin (Ig) variable (V) genes was evaluated in leukaemic cells from a B-cell chronic lymphocytic leukaemia (B-CLL) case over a 2-year period at four time points. Intraclonal heterogeneity was analysed by sequencing 305 molecular clones derived from polymerase chain reaction amplification of B-CLL cell IgV heavy (H) and light (C) chain gene rearrangements. Sequences were compared with evaluating intraclonal variation and the nature of somatic mutations. Although IgV intraclonal variation was detected at all time points, its level decreased with time and a parallel emergence of two more represented VHDJH clones was observed. They differed by nine nucleotide substitutions one of which only caused a conservative replacement aminoacid change. In addition, one VLJL rearrangement became more represented over time. Analyses of somatic mutations suggest antigen selection and impairment of negative selection of neoplastic cells. In addition, a genealogical tree representing a model of clonal evolution of the neoplastic cells was created. It is of note that, during the period of study, the patient showed clinical progression of disease. We conclude that antigen stimulation and somatic hypermutation may participate in disease progression through the selection and expansion of neoplastic subclone(s). [source] Chronic mucocutaneous candidiasis may cause elevated gliadin antibodiesACTA PAEDIATRICA, Issue 10 2009Florian Brinkert Abstract We present a 4-year-old boy admitted to the hospital due to the typical symptoms of celiac disease with severe dystrophy, anaemia and elevated gliadin IgG antibodies. Upper endoscopy ruled out celiac disease but showed severe Candida esophagitis. Due to an impaired T-cell function especially following Candida antigen stimulation in vitro, plus recurrent Candida infections of the skin, the diagnosis of chronic mucocutaneous candidasis (CMC) was made. Under the treatment with fluconazol, trimethoprim/sulfmethoxazole and IVIG, the child improved impressively. Gliadin antibodies declined steadily. Conclusion:, The common symptoms growth retardation, anaemia and elevated gliadin antibodies are suggestive for celiac disease but very unspecific. The rare immunodeficiency CMC may cause elevated gliadin antibodies. [source] | ||||||||||