INFLUENCE OF DONOR LYMPHOCYTES ON THE INCIDENCE OF PRIMARY GRAFT FAILURE AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION IN A MURINE MODEL

We used a murine model to determine the impact of donor lymphocyte sub sets on the incidence of primary marrow graft failure after transplant ation of lymphocyte-depleted bone marrow. After lethal irradiation wit h 7.5 Gy, Balb/c mice received 1 x 10(5) to 4 x 10(7) GvH-nonreactive (C57 x Balb)F1 or GvH-reactive C57Bl/6 marrow cells. Pretreatment with anti-Thy-1.2, anti-CD4/CD8, anti-asialo-GM1 or L-leucyl-L-leucine met hyl ester (Leu-Leu-OMe) was employed to eliminate T lymphocytes and/or natural killer cells, Primary graft failure was defined as death with neutrophils < 0.5 x 10(9)/l. To assess long-term chimaerism, the perc entage of H-2(b)-positive spleen cells was determined. Pretreatment wi th anti-Thy-1.2, anti-CD4/CD8 or Leu-Leu-OMe successfully eliminated G vHR-induced mortality. Graft failure rates gradually declined from 88% after transplantation of 1 x 10(5) cells to 0% after transplantation of 4 x 10(7) C57Bl/6 cells. The incidence of graft failure, however, w as not altered by T-celI depletion, provided that the unspecific loss of marrow cells was compensated for. After transplantation of GvH-nonr eactive (C57 x Balb)F1 bone marrow, neither ex-vivo treatment with ant i-Thy-1.2 and anti-asialo GM1 nor addition of 1 x 10(7) donor thymocyt es to the allograft significantly influenced engraftment. The data obt ained in our animal model suggest that the total number of marrow cell s is of critical importance for successful marrow engraftment and not the presence or absence of T cells, NK cells or GVHR.