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.
DR-BB Rat Thymus Contains Thymocyte Populations Predisposed to Autoreactivity
FITC, fluorescein isothiocyanate; IDDM, insulin-dependent diabetes mellitus; KRV, Kilham's rat virus; mAb, monoclonal antibody; MHC, major histocompatibility complex; PE, phycoerythrin; poly(T·C), polyinosinic acid–polycytidylic acid; SA, streptavidin; TCR, T-cell receptor.
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Barbara J Whalen, Aldo A Rossini, John P Mordes, Dale L Greiner; DR-BB Rat Thymus Contains Thymocyte Populations Predisposed to Autoreactivity. Diabetes 1 August 1995; 44 (8): 963–967. https://doi.org/10.2337/diab.44.8.963
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