Y. Zhao et al., IMMUNE RESTORATION BY FETAL PIG THYMUS GRAFTS IN T-CELL-DEPLETED, THYMECTOMIZED MICE, The Journal of immunology, 158(4), 1997, pp. 1641-1649
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.