Prevention of graft rejection by donor type II CD8⁺ T Cells (Tc2 cells) is not sufficient to improve engraftment in fetal transplantation

Objectives: Tc2 cells, a subset of CD8⁺ T cells, are able to facilitate engraftment in a murine model of postnatal allogeneic bone marrow transplantation. The purpose of this study was to evaluate whether Tc2 cells could improve engraftment in fetal transplantation. Methods: Gestational day 13 C57BL/6 (H-2^b) fetal mice were used as recipients, adult B6D2F ₁ mice (C57BL/6 x DBA/2, H-2^b/d) as donors, and splenocytes from B6C3F₁ (C57BL/6 x C3H/He, H-2^b/k) mice were used as stimulators in cultures used to generate the Tc2 cells from B6D2F₁ mice. Peripheral blood chimerism was examined monthly for 3 months. Thereafter, recipients were sacrificed to evaluate the levels of peritoneal, splenic and bone marrow chimerism. The T-cell responses of recipient splenocytes to cells of host origin were measured as a proliferative response in mixed lymphocyte cultures. Results: Low levels of peripheral blood cell chimerism (<0.3%) were observed at 1 month of age, which declined further by 3 months of age. The levels of donor cells in the spleen, bone marrow and peritoneal cavity were usually not more than 0.05%. The peritoneal cavity tended to have higher levels of donor cells with 1 recipient sustaining as high as 25.03% at the age of 3 months. Higher peritoneal chimerism correlated with a lower donor-specific T-cell response. Conclusions: Transplantation of Tc2 cells was insufficient to improve bone marrow engraftment in utero, suggesting that graft rejection is not the major barrier to successful in utero transplantation. Donor cells can persist in the peritoneal cavity and might play an important role in inducing immune tolerance in fetuses.