T-cells expressing the RT6 surface alloantigen appear to perform important immunoregulatory functions in the rat. Diabetes-prone BB rats lack circulating RT6+ T-cells and spontaneously develop autoimmune diabetes mellitus and thyroiditis. The coisogenic diabetes-resistant BB rat does circulate RT6+ T-cells and is free of disease. Transfusions leading to engraftment of RT6+ T-cells prevent both diabetes and thyroiditis in the diabetes-prone rat. To investigate the absence of this subset in the lymphopenic BB rat, we used both molecular and biochemical procedures and made the following observations: 1) an mRNA encoding RT6 protein is present in diabetes-prone spleen cells; 2) nucleotide sequencing of this transcript reveals an intact coding sequence for the RT6.1 alloantigen; 3) sensitive chemiluminescent assay of diabetes-prone lymph node cell detergent extracts shows that diabetes-prone RT6 mRNA is translated in vivo; 4) quantitatively, diabetes-prone lymph node cells express ≤ 10% of the RT6.1 protein found on similar numbers of diabetes-resistant BB cells; and 5) finally, we obtained evidence of an intact phosphatidylinositol linkage of the molecule to the cell surface and successfully immunoprecipitated the phosphatidylinositol-linked protein with DS4.23 monoclonal antibody, indicating that the RT6.1 antigen is correctly processed and folded in diabetes-prone lymph node cells. We conclude that the near total absence of RT6+ T-cells in the diabetes-prone BB rat is unlikely to be because of a defect in RT6 gene expression per se. Defects in RT6 gene regulation or other cellular defects leading to premature cell death in the T-cell lineage, alone or in combination, may instead be responsible.
An RT6a Gene Is Transcribed and Translated in Lymphopenic Diabetes-Prone BB Rats
Laura Crisá, Probir Sarkar, Debra J Waite, Friedrich Haag Friedrich, T V Rajan, John P Mordes, Eugene S Handler, Heinz-Günter Thiele, Aldo A Rossini, Dale L Greiner; An RT6a Gene Is Transcribed and Translated in Lymphopenic Diabetes-Prone BB Rats. Diabetes 1 May 1993; 42 (5): 688–695. https://doi.org/10.2337/diab.42.5.688
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