AN RT6A GENE IS TRANSCRIBED AND TRANSLATED IN LYMPHOPENIC DIABETES-PRONE BB RATS

T-cells expressing the RT6 surface alloantigen appear to perform impor tant immunoregulatory functions in the rat. Diabetes-prone BB rats lac k circulating RT6+ T-cells and spontaneously develop autoimmune diabet es mellitus and thyroiditis. The coisogenic diabetes-resistant BB rat does circulate RT6+ T-cells and is free of disease. Transfusions leadi ng to engraftment of RT6+ T-cells prevent both diabetes and thyroiditi s in the diabetes-prone rat. To investigate the absence of this subset in the lymphopenic BB rat, we used both molecular and biochemical pro cedures and made the following observations: 1) an mRNA encoding RT6 p rotein is present in diabetes-prone spleen cells; 2) nucleotide sequen cing of this transcript reveals an intact coding sequence for the RT6. 1 alloantigen; 3) sensitive chemiluminescent assay of diabetes-prone l ymph node cell detergent extracts shows that diabetes-prone RT6 mRNA i s translated in vivo; 4) quantitatively, diabetes-prone lymph node cel ls express less-than-or-equal-to 10% of the RT6.1 protein found on sim ilar numbers of diabetes-resistant BB cells; and 5) finally, we obtain ed evidence of an intact phosphatidylinositol linkage of the molecule to the cell surface and successfully immunoprecipitated the phosphatid ylinositol-linked protein with DS4.23 monoclonal antibody, indicating that the RT6.1 antigen is correctly processed and folded in diabetes-p rone 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 d efect 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.