TREATMENT OF SEVERE COMBINED IMMUNODEFICIENCY MICE WITH ANTIMURINE GRANULOCYTE MONOCLONAL-ANTIBODY IMPROVES HUMAN-LEUKOCYTE XENOTRANSPLANTATION

Background. The residual resistance of severe combined immunodeficienc y (SCID) mice to human graft is the main factor in conditioning both t he extent of human cell reconstitution and the xenograft-to-xenograft variability. We have recently shown that an early and massive murine g ranulocyte recruitment is the main event in the SCID mouse reaction to the human graft. Methods. Here, we evaluate the importance of mouse g ranulocytes in the restriction of human cell engraftment in SCID mice. We injected SCID mice with a monoclonal antibody to murine granulocyt es. Results, Injection of this antibody resulted in a marked depletion of polymorphonuclear cells in the hematopoietic organs of SCID mice, This depletion was associated with a significant increase in both the growth of human cell lines of different hematopoietic origin and the e ngraftment of human peripheral blood leukocytes. Moreover, the abolish ment of the early granulocyte reaction markedly reduced the xenograft- to-xenograft variation, a major shortcoming of these xenochimeric mode ls. Conclusions, These results provide new insights into the control o f the natural immune response of SCID mice against human graft, Furthe rmore, treatments aimed at controlling the acute inflammatory reaction of SCID mouse-to-human cell transplantation can be considered useful experimental approaches for increasing the xenograft-to-xenograft repr oducibility.