THE THYMUS CONTAINS A HIGH-FREQUENCY OF CELLS THAT PREVENT AUTOIMMUNEDIABETES ON TRANSFER INTO PREDIABETIC RECIPIENTS

Rats of the PVG.RT1(u) strain develop autoimmune diabetes when thymect omized at 6 wk of age and are rendered relatively lymphopenic by a cum ulative dose of 1,000 rads Cs-137 gamma-irradiation given in four spli t 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 cell s have a memory phenotype and are presumably primed to some extrathymi c 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) o f these cells protect similar to 50% of recipients and the level of pr otection increases with cell dose. It appears that one characteristic of the intrathymic selection of the T cell repertoire is the generatio n of cells that regulate the autoimmune potential of peripheral T cell s that have been neither clonally deleted intrathymically nor rendered irreversibly anergic in the periphery.