S. Ramanathan et P. Poussier, T cell reconstitution of BB/W rats after the initiation of insulitis precipitates the onset of diabetes, J IMMUNOL, 162(9), 1999, pp. 5134-5142
One of the diabetes susceptibility genes of the BB/W (Biobreeding/Worcester
) rat maps to the lyp locus on chromosome 4, The BB/W lyp allele is respons
ible for a severe peripheral T lymphopenia, Correction of this lymphopenia
by transfer of normal, histocompatible T cells prevents diabetes, providing
T cell reconstitution is initiated before insulitis, We have analyzed this
time-dependent regulation of the diabetogenic process by normal T cells, W
e demonstrate that T cell reconstitution after the initiation of insulitis
precipitates the onset of diabetes through the recruitment of donor T cells
to the autoimmune process, This inability of normal T cells to regulate pr
imed diabetogenic BB/W T cells and their own autoreactive potential a ere o
bserved when normal T cells outnumbered pathogenic T cells by approximately
1000-fold. Analysis of donor-derived T cells recovered from BB/W rats that
were reconstituted before insulitis, and hence protected from diabetes, de
monstrates that early T cell reconstitution of BB/W rats does not result in
a long term physical or functional depletion of islet cell-specific T cell
precursors among donor cells or in the expansion of T cells that can regul
ate the activation and expansion of diabetogenic T cells.