Haploidentical donor T cells fail to facilitate engraftment but lessen the immune response of host T cells in murine fetal transplantation.
The effects of donor T cells, or their CD8+ subset, on engraftment and tolerance induction in fetal transplantation were evaluated using an F1-into-parent mouse-model that does not permit a graft-versus-host effect. Gestational day 13 C57BL/6 (H-2Kb) fetuses were transplanted with B6D2F1 (H-2Kb/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.
Chen
Jeng-Chang
JC
Fetal Treatment Center, Department of Surgery, University of California, San Francisco, CA 94143-0793, USA.
Chang
Ming-Ling
ML
Lee
Hanmin
H
Muench
Marcus O
MO
D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002678:Chimera; D005260:Female; D005333:Fetus / Q000276:immunology*; D006087:Graft vs Host Reaction; D007108:Immune Tolerance; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D011247:Pregnancy; D013601:T-Lymphocytes / Q000276:immunology*