The long-term effects of parent-into-F1 graft-versus-host reaction (GVHR) was investigated by following splenic T cell markers and function for up to 18 months after GVHR induction. Despite the appearance of adequate numbers of T cells which expressed the normal compliment of T lymphocyte markers, these cells still failed to generate MHC self-restricted, CD4-mediated T helper responses. This defect was not due to suppression or a defect in antigen-presenting cell function. Analysis of donor chimerism in parent-into-F1 GVHR indicated three phases of repopulation: an expansion phase of donor T cells; a phase of host cell destruction; and a donor repopulation phase in which extensive donor cell repopulation is observed. Donor T cells that induce GVHR were studied for T cell receptor repertoire by Vbeta analyses. It was observed that donor T cell expressing the Vbeta markers of antihost reactivity were selectively expanded during GVHR. Vbeta analysis was also used to investigate the possible synergy between class I GVHR and donor-antihost m1s recognition. It was found that donor-antihost recognition of class I H-2 and m1s(a) resulted in acute GVHR, and preferential expansion of the Vbeta T cell receptor reactive with m1s(a). Depletion of these Vbeta T cells resulted in reduced donor chimerism, but not in abrogation of GVH-induced immune deficiency.
