IMMUNE RESTORATION BY FETAL PIG THYMUS GRAFTS IN T-CELL-DEPLETED, THYMECTOMIZED MICE

Donor-specific tolerance can be induced across a discordant xenogeneic barrier in T/NK cell-depleted, thymectomized (ATX) B10 mice by grafti ng of fetal pig thymic and liver tissue (FP THY/LIV) under the kidney capsule. We have now examined the phenotype and function of murine T c ells that develop in FP THY/LIV grafts in these mice. Mouse CD4(+) T c ells reached normal levels in PBL by 14 wk, and were maintained up to 30 wk. Similar proportions of splenic CD4(+) cells expressed the naive phenotype (CD45RB(high)MEL-14(+)CD44(low)) in FP THY/LIV graft recipi ents and euthymic control mice. These CD4 cells were functional, demon strating normal proliferative responses and up-regulation of CD25 and CD69 after activation by mitogens or alloantigens. They proliferated i n response to the protein Ag KLH presented by host MHC following in vi vo immunization. ATX B10 mice grafted with FP THY/LIV also cleared Pne umocystis carinii infections, whereas simultaneously-treated ATX B10 m ice not receiving FP THY were unable to do so. Discordant xenogeneic t hymus grafting can therefore restore immune competence. Thus, in addit ion to tolerance induction, xenogeneic thymic replacement might have a potential role in the reconstitution of immunity in patients afflicte d with immunodeficiencies affecting the thymus.