UCSF

The effects of donor T cells, or their CD8(+) subset, on engraftment and tolerance induction in fetal transplantation were evaluated using an F-1-into-parent mouse-model that does not permit a graft-versus-host effect. Gestational day 13 C57BL/6 (H-2K(b)) fetuses were transplanted with B6D2F(1) (H-2K(b/d)) light density bone marrow cells (LDBMC) containing 1-2% T cells, T-cell depleted bone marrow cells (TDBMC, <0.1% T cells), or TDBMC with enriched CD8(+) T cells (CD8). Chimaerism levels in the peripheral blood, spleen and bone marrow were usually below 0.2% in all groups, indicating that T cells do not improve engraftment without a graft-versus-host effect. A significant, but transient, wave of donor cells was seen in the peripheral blood at 1 month of age in the CD8 and LDBMC groups. Relatively high levels of chimaerism (<17%) were sometimes detected in the peritoneal cavities of recipients. T-cell tolerance specific to donor cells was evaluated in mixed lymphocyte cultures. The CD8 and LDBMC groups had significantly lower T-cell responses than untransplanted controls. These findings indicate that in utero transplantation of haploidentical donor CD8(+) or CD3(+) cells can help to lessen the immune response of host T cells towards donor cells. The persistence of donor cells in the peritoneal cavity also correlated with tolerance induction.