More MS news articles for May 2002

A T-Cell Functional Phenotype Common among Autoimmune-Prone Rodent Strains

Scand J Immunol 2002 Jun;55(6):546-59
Lang J, Bellgrau D.
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, USA.

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.