Recovery of T cell populations after acute graft-vs-host reaction.

We previously have observed that T dependent immune functions were deficient for several months after induction of acute suppressive graft-vs-host-reaction (GVHR) by injection of parental C57BL/10 donor spleen cells into unirradiated (B10 x B10.BR) F, hosts. We therefore investigated whether new T cells matured after acute GVHR, and whether these were tolerant of host Ag. By 8 to 17 mo after GVHR, the frequencies of splenic CD4 and CD8 T cells were found to be comparable to age-matched untreated hosts, although the lymphoid organ size and hence the total number of T cells was significantly reduced. When GVHR was induced with a combination of C57BL/6 (Thy-1.2) mature lymphocytes and B6.PL (Thy-1.1) bone marrow stem cells, the mature donor Thy-1.2 T cells initially predominated during the acute GVHR. After several months, however, 75% of the CD4 and 50% of the CD8 T cell population was derived from donor Thy-1.1% pre-T cells that had matured in the host. Long term GVHR spleen cells were unresponsive to host Ag in CTL assays, but did not suppress anti-host CTL responses. Finally, host-reactive V beta 11 TCR expressing cells were found to be clonally deleted from splenic CD4 and CD8 populations, consistent with intrathymic negative selection. This evidence suggests that the post-GVHR thymus has the capacity to produce and negatively select phenotypically mature CD4 and CD8 T cells and that a failure to clonally delete self-reactive populations is not a contributing factor to the development of chronic GVHR in this system.