Cytotoxic T-cell precursors with low-level CD8 in the diabetes-prone Biobreeding rat: implications for generation of an autoimmune T-cell repertoire.
Lymphocytes from diabetes-prone Biobreeding rats consistently fail to generate T-cell-mediated cytotoxicity under conditions where cytotoxic T lymphocyte activity is readily demonstrated in normal rats. The failure is associated with generalized T-cell lymphopenia and marked reduction in the frequency of CD8+ cells. The few remaining CD8+ cells are widely held to be natural killer cells rather than class I major histocompatibility complex-restricted T lymphocytes. In this report we show that a detectable percentage of CD8+ lymphocytes express the T-cell receptor for antigen, thus identifying them as part of the T-cell lineage. The failure of these CD8+ T-cell-receptor-positive T cells to lyse target cells that are susceptible to T-cell mediated cytotoxicity is associated with markedly reduced expression of cell-surface CD8. Targets expressing higher than normal levels of class I major histocompatibility complex target antigen could be lysed, suggesting that reduction in CD8 has decreased T-cell activity for target antigen. We discuss the derivation of T cells that express low levels of CD8 and the role they could play in generating autoimmune diabetes.
Bellgrau
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Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver 80262.
Lagarde
A C
AC
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D015551:Autoimmunity; D016827:CD8 Antigens; D003602:Cytotoxicity, Immunologic; D003921:Diabetes Mellitus, Experimental / Q000276:immunology; D004198:Disease Susceptibility; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D010641:Phenotype; D051381:Rats; D011913:Rats, Inbred BB / Q000276:immunology*; D011917:Rats, Inbred Lew / Q000276:immunology; D011919:Rats, Inbred Strains / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I