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A T‐Cell Functional Phenotype Common among Autoimmune‐Prone Rodent Strains
Author(s) -
Lang J.,
Bellgrau D.
Publication year - 2002
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.2002.01086.x
Subject(s) - autoimmunity , biology , phenotype , immunology , t cell receptor , cd8 , autoimmune disease , negative selection , t cell , downregulation and upregulation , genetics , antigen , gene , immune system , antibody , genome
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 F 1 , 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.