In murine allogeneic bone marrow transplantation recipients, treatment of the hosts with a nonmyeloablative regimen, including depleting anti-CD4 and anti-CD8 mAbs, allows establishment of long-term mixed chimerism and donor-specific tolerance. However, in the xenogeneic rat-to-mouse combination, additional anti-Thy1.2 and anti-NK1.1 mAbs are required. We have now attempted to identify the xenoresistant mouse cell populations that are targeted by anti-NK1.1 and anti-Thy1.2 mAbs. C57BL/6 (B6) wild-type, B6 TCRβ-/-, and B6 TCRδ-/- mice received anti-CD4 and anti-CD8 mAbs, followed by 3 Gy of whole body irradiation, 7 Gy of thymic irradiation, and transplantation of T cell-depleted rat bone marrow cells. Anti-NK1.1 and anti-Thy1.2 mAbs were additionally administered to some groups. Increased rat chimerism was observed in TCRδ-/- mice treated with anti-CD4, anti-CD8, and anti-NK1.1 mAbs compared with similarly treated TCRβ-/- mice. In TCRβ-/- mice, but not in TCR δ-/- mice, donor chimerism was increased by treatment with anti-Thy1.2 mAb, indicating that CD4-CD8-TCRγδ+Thy1.2+ NK1.1- cells (γδ T cells) are involved in the rejection of rat marrow. In addition, chimerism was enhanced in both TCRβ-/- and TCRδ-/- mice treated with anti-CD4, anti-CD8, and anti-Thy1.2 mAbs by the addition of anti-NK1.1 mAb to the conditioning regimen. Donor-specific skin graft prolongation was enhanced by anti-Thy1.2 and anti-NK1.1 mAbs in TCRδ-/- mice. Therefore, in addition to CD4 and CD8 T cells, γδ T cells and NK cells play a role in resisting engraftment of rat marrow and the induction of xenograft tolerance in mice.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of Immunology|
|State||Published - Jan 15 2001|
ASJC Scopus subject areas