Synergistic effects of in vivo depletion of Ly-49A and Ly-49G2 natural killer cell subsets in the rejection of H2^b bone marrow cell allografts

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, D(d), binding of which results in an inhibitory signal to the NK cell but allows them to lyse H2^b targets in vitro. We therefore examined the ability of these subsets to reject H2^b bone marrow cell allografts in lethally irradiated mice. Surprisingly, depletion of Ly-49A⁺ NK cells in BALB/c or B10.D2 mice (both H2(d)) had no effect on the rejection of H2^b BMC. However, Ly-49A depletion did partially abrogate the ability of B10.BR (H2(k)) mice to reject H2^b allografts. Although depletion of either Ly-49A⁺ or Ly-49G2⁺ NK cells alone had no effect on the ability of B10.D2 mice to reject H2^b 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 H2^b 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. (C) 2000 by The American Society of Hematology.