Requirement of the thymus for the recovery of anti-alloantigen helper T cells from tolerance induced by intravenous presensitization with allogeneic cells.

Intravenous presensitization of C57BL/6 (B6) mice with class I H-2-disparate B6-C-H-2bm1 (bm1) whole spleen cells and class II H-2-disparate B6-C-H-2bm12 (bm12) spleen cells depleted of APC resulted in almost complete elimination of the respective anti-bm1 and anti-bm12 reactivities. However, the reduced alloreactivities as assessed by Th cell capacities (proliferative responses and IL-2 production) were recovered around 8 wk after the i.v. presensitization in euthymic B6 mice. In contrast, background levels of bm1- or bm12-specific reactivities were revealed to last more than 12 wk after the presensitization in B6 mice which had been thymectomized prior to the i.v. presensitization. Such a reduced alloreactivity was also observed in the capacity to reject bm1 or bm12 skin grafts, and prolongation of graft survival was strikingly enhanced in the thymectomized group compared to that induced in the nonthymectomized group. However, there was an important difference in such prolongation in the thymectomized hosts between bm1 and bm12 grafts; a considerable percentage (greater than 80%) of bm12 skin grafts continued to take more than 5 mo, whereas about 90% of bm1 grafts were rejected by around 5 mo along with the emergence of weak, but detectable anti-bm1 Th and cytotoxic T cell activities. These results indicate that 1) i.v. presensitization regimen is capable of eliminating in vitro and in vivo alloreactive capabilities but these alloreactivities can be recovered in euthymic hosts with T cell repopulating potential and 2) there are differential requirements of the thymus for repopulating anti-bm1 (Lyt-2+) and anti-bm12 (L3T4+) T cell activities.