Synergistic effects of in vivo depletion of Ly-49A and Ly-49G2 natural killer cell subsets in the rejection of H2b bone marrow cell allografts

Abstract

Abstract Subsets of murine natural killer (NK) cells exist that express the Ly-49 family of molecules that recognize different major histocompatibility complex (MHC) determinants. Bone marrow transplantation studies were performed to examine the in vivo functions of 2 of these subsets. Subsets of Ly-49A and Ly-49G2 NK share specificity for the same MHC class 1 ligand, Dd, binding of which results in an inhibitory signal to the NK cell but allows them to lyse H2b targets in vitro. We therefore examined the ability of these subsets to reject H2b bone marrow cell allografts in lethally irradiated mice. Surprisingly, depletion of Ly-49A+ NK cells in BALB/c or B10.D2 mice (both H2d) had no effect on the rejection of H2b BMC. However, Ly-49A depletion did partially abrogate the ability of B10.BR (H2k) mice to reject H2ballografts. Although depletion of either Ly-49A+ or Ly-49G2+ NK cells alone had no effect on the ability of B10.D2 mice to reject H2b BMC, depletion of both subsets dramatically and synergistically abrogated rejection. Studies with various B10 congenic mice and their F1 hybrids indicate that this synergy between Ly49A and Ly4G2 depletion occurs in every instance. Thus, Ly-49A+ NK cells appear to play a role in the rejection H2b bone marrow allografts, but, in most strains of mice studied, Ly-49G2+ NK cells must also be eliminated. The putative roles of these NK cell subsets in clinical transplantation remains to be elucidated.