CD4(+)CD8(-) thymocytes that express L-selectin protect rats from diabetes upon adoptive transfer

Previous studies have shown that insulin-dependent diabetes can be induced in normal PVG.RT1(u) rats by a protocol of adult thymectomy and irradiation. The injection of CD4(+) T cells from non-irradiated syngeneic donors prevents the onset of disease in approximately 50 % of pre-diabetic recipients but all rats are protected if a particular subset of CD4(+) cells is transferred. These protective cells express TCR alpha beta and have a memory phenotype, being CD45RC(low) RT6(+). Further studies have demonstrated that the transfer of CD4(+)CD8(-) thymocytes, like that of unfractionated CD4(+) peripheral T cells, also protects approximately half of recipients from diabetes suggesting that, as with the peripheral T cells, a functional heterogeneity may exist amongst CD4(+)CD8(-) thymocytes. In this study, we show that L-selectin is expressed bg 50-60 % of all CD4(+)CD8(-) thymocytes from 6-week-old rats. Adoptive transfer of these populations into thymectomized and irradiated rats revealed that the protection from diabetes observed by CD4(+)CD8(-) thymocytes was mediated almost entirely by the L-selectin(+) subset. Cells with this phenotype were also able to mediate both humoral and cell mediated responses, providing primed B cells with help for secondary antibody responses and mediating local graft-versus-host reactions. L-selectin(-)CD4(+)CD8(-) thymocytes failed to mediate these responses. These data indicate that CD4(+)CD8(-) thymocytes must mature to the stage of L-selectin expression, before they can mediate normal T cell function. The implications of these results an discussed with respect to the possible role of murine NK1.1(+) thymocytes in the control oi autoimmunity.