PECULIAR T-CELL SIGNALING DOES NOT PRECLUDE POSITIVE SELECTION IN THE DIABETES-PRONE BB RAT

Various studies have provided evidence that peripheral T-cells from the diabetes-prone BB-DP rat are abnormal in function and cell surface phenotype. These characteristics have often been interpreted as indicators of immaturity and/or short life span. In this study, we describe a CD4-dependent signaling abnormality in BB-DP peripheral T-cells. In spite of the fact that CD4 plays a critical role in thymocyte development, the abnormal signaling does not appear to influence thymocyte development at the stage when the T-cell receptor is rearranged and the recombinase enzymes RAG-1 and RAG-2 transcripts are downregulated. Therefore, if a maturation defect reading to the seeding of the periphery with immature T-cells occurs in the BB-DP rat, it does not preclude the initial selection of the self major histocompatibility complex-restricted T-cell repertoire.