T cell reconstitution of BB/W rats after the initiation of insulitis precipitates the onset of diabetes.
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 responsible 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. We 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 primed diabetogenic BB/W T cells and their own autoreactive potential were observed 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, demonstrates 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 regulate the activation and expansion of diabetogenic T cells.
Ramanathan
S
S
Department of Immunology, University of Toronto, Ontario, Canada.
Poussier
P
P
D036002:ADP Ribose Transferases / Q000032:analysis; D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D020296:Animals, Congenic; D000945:Antigens, Differentiation, T-Lymphocyte; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control; D020022:Genetic Predisposition to Disease / Q000276:immunology; D007275:Injections, Intravenous; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology*; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D017710:Lymphocyte Transfusion / Q000379:methods; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D051381:Rats; D011913:Rats, Inbred BB; D011920:Rats, Inbred WF; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D013997:Time Factors
D000945:Antigens, Differentiation, T-Lymphocyte; D008562:Membrane Glycoproteins; D036002:ADP Ribose Transferases; C090163:Art2b protein, rat