The Thymus Contains a High Frequency of Cells that Prevent Autoimmune Diabetes on Transfer into Prediabetic Recipients

Rats of the PVG.RT1(u) strain develop autoimmune diabetes when thymectomized at 6 wk of age and are rendered relatively lymphopenic by a cumulative dose of 1,000 rads (137)Cs γ-irradiation given in four split doses. Previous studies have shown that the disease is prevented by the intravenous injection of 5 × 10(6) CD4(+) CD45RC(−) TCRαβ(+) 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 × 10(5) of these cells protect ∼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.