A T-cell functional phenotype common among autoimmune-prone rodent strains.
The genetic basis and familial clustering of autoimmunity suggest that common phenotypic traits predispose individuals to disease. We found a hyporesponsive T-cell phenotype that was shared by all autoimmune-prone mouse and rat strains tested, including MRL, nonobese diabetic (NOD), NZB, NZW, NZB/W F1, SJL and SWR mice, as well as DA and BB rats, but was not evident in nonautoimmune-prone rodents. This T-cell intrinsic, age-independent hyporesponsiveness is measured as an increased activation threshold for upregulation of activation markers upon T-cell receptor (TCR) cross-linking both in vitro and in vivo. Inefficient deletion of CD4 and CD8 single-positive, heat stable antigen (HSA)hi medullary thymocytes was also observed in hyporesponsive donors. We interpret these data to suggest that increased TCR-mediated signalling thresholds in autoimmune-prone individuals may contribute to the escape of autoreactive thymocytes from negative selection.
Lang
J
J
Barbara Davis Center for Childhood Diabetes and the Integrated Department of Immunology, University of Colorado Health Sciences Center and National Jewish Medical and Research Center, Denver, Colorado, USA. julie.lang@uchsc.edu
Bellgrau
D
D
D000818:Animals; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D020412:Multifactorial Inheritance / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D051381:Rats; D011913:Rats, Inbred BB; D011916:Rats, Inbred F344; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D011948:Receptors, Antigen, T-Cell