DR-BB Rat Thymus Contains Thymocyte Populations Predisposed to Autoreactivity

  1. Dale L Greiner
  1. Department of Medicine, University of Massachusetts Medical School Worcester, Massachusetts
  1. Address correspondence and reprint requests to Dr. Dale L. Greiner, Diabetes Division, Biotech 2, 373 Plantation St., Worcester, MA 01605.

Abstract

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.

  • Received February 6, 1995.
  • Revision received April 5, 1995.
  • Accepted April 5, 1995.
| Table of Contents