Murine Natural Killer Cells and Marrow Graft Rejection

Abstract

Rejection of bone marrow transplants in lethally irradiated mice differs from rejection of solid tissue grafts in several respects. The genetic laws that govern rejection of solid tissue grafts often fail with hemopoietic grafts. For example, F1 hybrids between two H-2 disparate strains of mice often reject parental bone marrow cells (BMC), and conversely, marrow cells of F1 hybrids (H-2 heterozygous) are usually not rejected by either parent or an unrelated allogeneic recipient. Thus, unlike the classical MHC antigens, the hemopoietic histocompatibility (Hh) antigens relevant marrow graft rejection are inherited in a recessive pattern. The major Hh (Hh-1) locus maps within the mouse H-2 complex between the H-2S and H-2D regions, and it can therefore be dissociated from the class-I MHC genes. Nevertheless, it is possible that class-I MHC antigens play a role in the formation or expression of Hh-1 antigens. Three models that explain the possible relationship between class-I MHC and Hh-1 genes and the noncodominant pattern of inheritance of Hh antigens are presented. The effector cells responsible for resisting BMC grafts are different from those responsible for rejection of solid tissue grafts. Three cell types, natural killer cells (CD3-, NK1.1+), cytotoxic T cells (CD3+, CD8+), and T cells with natural killer cell markers (CD3+, NK1.1+) have been implicated in the rejection of BMC grafts. Involvement of these cell types is reviewed and the relative roles played by each are discussed. Evidence supporting the existence of Hh-1 specific subsets of NK cells is presented.