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Knowing the autoantigen target(s) in an organ-specific autoimmune disease is essential to understanding its pathogenesis. Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease characterized by lymphocytic infiltration of the islets of Langerhans (insulitis) and destruction of insulin-secreting pancreatic beta-cells. Several beta-cell proteins(More)
OBJECTIVE It is well established that the primary mediators of beta-cell destruction in type 1 diabetes are T-cells. Nevertheless, the molecular basis for recognition of beta-cell-specific epitopes by pathogenic T-cells remains ill defined; we seek to further explore this issue. RESEARCH DESIGN AND METHODS To determine the properties of beta-cell-specific(More)
Studies of rodent models and preliminary studies in Chapel Hill, North Carolina 27599 man have shown that the completion of ␤ cell destruc-† Department of Microbiology and Immunology tion can be considerably delayed or prevented by paren-Department of Medicine teral administration of ␤ cell autoantigens—including School of Medicine insulin, glutamic acid(More)
Natural CD4(+)CD25(+) regulatory T (CD4(+)CD25(+) T reg) cells play a key role in the immunoregulation of autoimmunity. However, little is known about the interactions between CD4(+)CD25(+) T reg cells and autoreactive T cells. This is due, in part, to the difficulty of using cell surface markers to identify CD4(+)CD25(+) T reg cells accurately. Using a(More)
Tumor necrosis factor (TNF) alpha is a cytokine that has potent immune regulatory functions. To assess the potential role of this cytokine in the early development of autoimmunity, we investigated the effect of TNF on the development of insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice, a spontaneous murine model for autoimmune,(More)
Self-antigens expressed by apoptotic cells (ACs) may become targets for autoimmunity. Tolerance to these antigens is partly established by an ill-defined capacity of ACs to inhibit antigen-presenting cells such as dendritic cells (DCs). We present evidence that the receptor tyrosine kinase Mer (MerTK) has a key role in mediating AC-induced inhibition of DC(More)
Tumor necrosis factor (TNF) ot is a cytokine that has potent immune regulatory functions. To assess the potential role of this cytokine in the early development of autoimmunity, we investigated the effect of TNF on the development of insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice, a spontaneous murine model for autoimmune,(More)
An immunogenic peptide (GP2) derived from HER-2/neu binds to HLA-A2.1 very poorly. Some altered-peptide ligands (APL) of GP2 have increased binding affinity and generate improved cytotoxic T lymphocyte recognition of GP2-presenting tumor cells, but most do not. Increases in binding affinity of single-substitution APL are not additive in double-substitution(More)
Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease characterized by the destruction of the insulin-secreting beta cells found in the islets of Langerhans. Reduced beta-cell mass results in overt diabetes, requiring lifelong exogenous insulin administration and the possibility of numerous sequelae. Incidence and development of IDDM depend(More)
Residual β-cells found at the time of clinical onset of type 1 diabetes are sufficient to control hyperglycemia if rescued from ongoing autoimmune destruction. The challenge, however, is to develop an immunotherapy that not only selectively suppresses the diabetogenic response and efficiently reverses diabetes, but also establishes long-term β-cell-specific(More)