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 leading 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.
Bellgrau
D
D
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver.
Redd
J M
JM
Sellins
K S
KS
D000818:Animals; D017209:Apoptosis; D015704:CD4 Antigens / Q000276:immunology; D004254:DNA Nucleotidyltransferases / Q000096:biosynthesis; D004268:DNA-Binding Proteins; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D015329:Gene Rearrangement, T-Lymphocyte; D018398:Homeodomain Proteins; D019426:Integrases; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D014176:Protein Biosynthesis; D011506:Proteins / Q000032:analysis; D051381:Rats; D011913:Rats, Inbred BB / Q000276:immunology*; D011920:Rats, Inbred WF; D045522:Recombinases; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic
D015704:CD4 Antigens; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D011506:Proteins; D045522:Recombinases; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D004254:DNA Nucleotidyltransferases; D019426:Integrases; C115006:integron integrase IntI1