Diabetes, Vol 44, Issue 8 963-967, Copyright © 1995 by American Diabetes Association

ARTICLES

DR-BB rat thymus contains thymocyte populations predisposed to autoreactivity

BJ Whalen, AA Rossini, JP Mordes and DL Greiner
Department of Medicine, University of Massachusetts Medical School, Worcester, USA.

We have induced autoimmune insulin-dependent diabetes mellitus (IDDM) in athymic WAG rats by transfusing thymocytes from histocompatible phenotypically normal rats of the DR-BB strain. DR-BB rats rarely develop spontaneous IDDM, but readily become hyperglycemic if depleted in vivo of regulatory T-cells that express the RT6.1 maturational alloantigen. Successful adoptive transfer of IDDM by DR-BB thymocytes required that the athymic recipients be depleted of emerging populations of donor-origin RT6.1+ T-cells. Thymocytes from both normal and RT6-depleted diabetic DR donors were equally capable of transferring autoimmunity. In contrast, thymocytes from normal histocompatible YOS rats failed to transfer IDDM. The autoreactive potential of DR-BB rat thymocytes was minimal from birth to 4 weeks of age and then increased substantially at 8-9 weeks of age. These results demonstrate that the DR-BB rat thymus harbors abnormal cell populations predisposed to autoreactivity. The data localize the developmental defect leading to diabetes in the BB rat to an abnormal intrathymic selection process.
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