A. Saoudi et al., THE THYMUS CONTAINS A HIGH-FREQUENCY OF CELLS THAT PREVENT AUTOIMMUNEDIABETES ON TRANSFER INTO PREDIABETIC RECIPIENTS, The Journal of experimental medicine, 184(6), 1996, pp. 2393-2398
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.