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Organ-specific Autoimmunity (organ-specific + autoimmunity)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Control of T-cell activation by CD4+ CD25+ suppressor T cells

IMMUNOLOGICAL REVIEWS, Issue 1 2001
Ethan M. Shevach
Summary: Depletion of the minor (,10%) subpopulation of CD4+ T cells that co-expresses CD25 (interleukin (IL)-2 receptor ,-chain) by thymectomy of neonates on the third day of life or by treatment of adult CD4+ T cells with anti-CD25 and complement results in the development of organ-specific autoimmunity. Autoimmune disease can be prevented by reconstitution of the animals with CD4+ CD25+ cells. CD4+ CD25+ -mediated protection of autoimmune gastritis does not require the suppressor cytokines IL-4, IL-10, or transforming growth factor (TGF)-,. Mice that express a transgenic T-cell receptor (TCR) derived from a thymectomized newborn that recognizes the gastric parietal cell antigen H/K ATPase all develop severe autoimmune gastritis very early in life. CD4+ CD25+ T cells are also powerful suppressors of the activation of both CD4+ and CD8+ T cells in vitro. Suppression is mediated by a cell contact-dependent, cytokine-independent T,T interaction. Activation of CD4+ CD25+ via their TCR generates suppressor effector cells that are capable of non-specifically suppressing the activation of any CD4+ or CD8+ T cell. Activation of suppressor effector function is independent of co-stimulation mediated by CD28/CTLA-4 interactions with CD80/CD86. We propose that CD4+ CD25+ T cells recognize organ-specific antigens, are recruited to sites of autoimmune damage where they are activated by their target antigen, and then physically interact with autoreactive CD4+ or CD8+ effector cells to suppress the development of autoimmune disease. [source]

Onset of promiscuous gene expression in murine fetal thymus organ culture

IMMUNOLOGY, Issue 3 2006
Renato Sousa Cardoso
Summary T-cell differentiation and induction of tolerance to self-antigens occurs mainly in the thymus. Thymic stromal cells, specifically medullary thymic epithelial cells, express a diverse set of genes encoding parenchymal organ-specific proteins. This phenomenon has been termed promiscuous gene expression (PGE) and has been implicated in preventing organ-specific autoimmunity by inducing T-cell tolerance to self antigens. Early thymopoiesis and the critical factors involved in T-cell differentiation can be reproduced in vitro by murine fetal thymus organ culture (FTOC), which mimics the natural thymic microenvironment. To evaluate the occurrence of PGE in FTOC, gene expression profiling during in vitro thymic development in BALB/c mice was performed using a set of nylon cDNA microarrays containing 9216 sequences. The statistical analysis of the microarray data (sam program) revealed the temporal repression and induction of 57 parenchymal and seven lymphoid organ-specific genes. Most of the genes analysed are repressed during early thymic development (15,17 days post-coitum). The expression of the autoimmune regulator (AIRE) gene at 16 days post-coitum marks the onset of PGE. This precedes the induction of parenchymal organ genes during the late developmental phase at 20 days post-coitum. The mechanism of T-cell tolerance induction begins during fetal development and continues into adulthood. Our findings are significant because they show a fine demarcation of PGE onset, which plays a central role in induction of T-cell tolerance. [source]

Tolerance and autoimmunity in the eye: a role for CD8 T cells in organ-specific autoimmunity in the retina

IMMUNOLOGY, Issue 3 2003
John V. Forrester
No abstract is available for this article. [source]

Reduced CD4+,CD25, T cell sensitivity to the suppressive function of CD4+,CD25high,CD127,/low regulatory T cells in patients with active systemic lupus erythematosus

ARTHRITIS & RHEUMATISM, Issue 7 2008
Ram Kumar Chowdary Venigalla
Objective CD4+,CD25high regulatory T (Treg) cells play a crucial role in the maintenance of self tolerance and prevention of organ-specific autoimmunity. The presence of many in vivo,preactivated CD4+,CD25++ T cells in patients with systemic lupus erythematosus (SLE) poses a difficulty in discriminating CD25++ activated T cells from CD25high Treg cells. To overcome this problem, we analyzed the phenotype and function of CD4+,CD25high,CD127,/low natural Treg (nTreg) cells isolated from the peripheral blood of patients with SLE. Methods CD4+,CD25high,CD127,/low nTreg cells and CD4+,CD25, responder T (Tresp) cells from patients with SLE and normal donors were separated by fluorescence-activated cell sorting. Cell proliferation was quantified by 3H-thymidine incorporation, and immunophenotyping of the cells was done using FACScan. Results Comparable percentages of CD4+,CD25high,FoxP3+ T cells were observed in patients with SLE and normal donors. Proliferation of SLE nTreg cells sorted into the subset CD4+,CD25high,CD127,/low was significantly decreased compared with that of SLE nTreg cells sorted into the subset CD4+,CD25high (mean ± SEM 2,223 ± 351 counts per minute versus 9,104 ± 1,720 cpm, respectively), while in normal donors, these values were 802 ± 177 cpm and 2,028 ± 548 cpm, respectively, confirming that effector cell contamination was reduced. Notably, the suppressive activity of nTreg cells was intact in all groups. However, CD4+,CD25, Tresp cells isolated from patients with active SLE were significantly less sensitive than those from patients with inactive SLE to the suppressive function of autologous or normal donor CD4+,CD25high,CD127,/low nTreg cells. Furthermore, a significant inverse correlation was observed between the extent of T cell regulation in suppressor assays and the level of lupus disease activity. Conclusion This study is the first to show that, in human SLE, impaired sensitivity of Tresp cells to the suppressive effects of a comparably functional, highly purified nTreg cell population leads to a defective suppression of T cell proliferation in active SLE. Studies aiming to define the mechanisms leading to Tresp cell resistance might help in the development of highly specific, alternative immunotherapeutic tools for the control of systemic autoimmune diseases such as SLE. [source]