The thymus contains a high frequency of cells that prevent autoimmune diabetes on transfer into prediabetic recipients.
Rats of the PVG.RT1u strain develop autoimmune diabetes when thymectomized at 6 wk of age and are rendered relatively lymphopenic by a cumulative dose of 1,000 rads 137Cs gamma-irradiation given in four split doses. Previous studies have shown that the disease is prevented by the intravenous injection of 5 x 10(6) CD4+ CD45RC-TCR alpha beta+ RT6+ peripheral T cells from normal syngeneic donors. These cells have a memory phenotype and are presumably primed to some extrathymic antigen. However, we now report that the CD4+ CD8- population of mature thymocytes is a very potent source of cells, with the capacity to prevent diabetes in our lymphopenic animals. As few as 6 x 10(5) of these cells protect approximately 50% of recipients and the level of protection increases with cell dose. It appears that one characteristic of the intrathymic selection of the T cell repertoire is the generation of cells that regulate the autoimmune potential of peripheral T cells that have been neither clonally deleted intrathymically nor rendered irreversibly anergic in the periphery.
Saoudi
A
A
Medical Research Council Cellular Immunology Unit, Sir William Dunn School of Pathology, University of Oxford, United Kingdom.
Seddon
B
B
Fowell
D
D
Mason
D
D
D036002:ADP Ribose Transferases; D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D001402:B-Lymphocytes / Q000276:immunology / Q000528:radiation effects; D015704:CD4 Antigens; D002588:Cesium Radioisotopes; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000517:prevention & control*; D005260:Female; D017493:Leukocyte Common Antigens; D008231:Lymphopenia; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D011236:Prediabetic State / Q000276:immunology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D051381:Rats; D011922:Rats, Mutant Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000528:radiation effects; D013934:Thymectomy; D013950:Thymus Gland / Q000276:immunology*; D014916:Whole-Body Irradiation
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D002588:Cesium Radioisotopes; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D036002:ADP Ribose Transferases; C449322:Art2a protein, mouse; C449339:Art2b protein, mouse; C090163:Art2b protein, rat; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1