Cytotoxic T-Cell Precursors with Low-Level CD8 in the Diabetes-Prone Biobreeding Rat: Implications for Generation of an Autoimmune T-Cell Repertoire

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 87; no. 1; pp. 313 - 317
• Main Authors: Bellgrau, Donald, Lagarde, Anne-Catherine
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.01.1990; National Acad Sciences
• Subjects: Animals; Antibodies; Antigens; Antigens, Differentiation, T-Lymphocyte - analysis; Autoimmunity; Biological and medical sciences; Blasts; CD8 Antigens; Cytotoxicity, Immunologic; Diabetes; Diabetes Mellitus, Experimental - immunology; Disease Susceptibility; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Histocompatibility Antigens Class I - analysis; Lymphocytes; Medical sciences; Natural killer cells; Phenotype; Rats; Rats, Inbred BB - immunology; Rats, Inbred Lew - immunology; Rats, Inbred Strains - immunology; T cell antigen receptors; T lymphocytes; T-Lymphocytes - immunology; T-Lymphocytes, Cytotoxic - immunology; Thymocytes; Type 1 diabetes mellitus; Autoimmunity; Endocrinopathy; T cell receptor; Rat; Rodentia; Biological marker; Cytotoxicity; Precursor; Vertebrata; Mammalia; T-Lymphocyte; Insulin dependent diabetes; Endocrine pancreatic diseases
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.87.1.313

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+lymphocyctes 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 avidity 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.