DR-BB rat thymus contains thymocyte populations predisposed to autoreactivity.
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.
Whalen
B J
BJ
Department of Medicine, University of Massachusetts Medical School, Worcester, USA.
Rossini
A A
AA
Mordes
J P
JP
Greiner
D L
DL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D016219:Immunotherapy, Adoptive; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion; D011070:Poly I-C / Q000494:pharmacology; D051381:Rats; D011913:Rats, Inbred BB; D011923:Rats, Nude; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D011070:Poly I-C