Treatment of severe combined immunodeficiency mice with anti-murine granulocyte monoclonal antibody improves human leukocyte xenotransplantation.

BACKGROUND: The residual resistance of severe combined immunodeficiency (SCID) mice to human graft is the main factor in conditioning both the extent of human cell reconstitution and the xenograft-to-xenograft variability. We have recently shown that an early and massive murine granulocyte recruitment is the main event in the SCID mouse reaction to the human graft.
METHODS: Here, we evaluate the importance of mouse granulocytes in the restriction of human cell engraftment in SCID mice. We injected SCID mice with a monoclonal antibody to murine granulocytes.
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 engraftment of human peripheral blood leukocytes. Moreover, the abolishment of the early granulocyte reaction markedly reduced the xenograft-to-xenograft variation, a major shortcoming of these xenochimeric models.
CONCLUSIONS: These results provide new insights into the control of the natural immune response of SCID mice against human graft. Furthermore, 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 reproducibility.