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 fa mily 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 o f which results in an inhibitory signal to the NK cell but allows them to l yse H2(b) targets in vitro. We therefore examined the ability of these subs ets 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 (b oth H2(d)) had no effect on the rejection of H2b BMC, However, Ly-49A deple tion 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 H2b BMC, deple tion of both subsets dramatically and synergistically abrogated rejection. Studies with various B10 congenic mice and their Fl hybrids indicate that t his synergy between Ly49A and Ly4G2 depletion occurs in every instance. Thu s, Ly-49A(+) NK cells appear to play a role in the rejection H2(b) bone mar row allografts, but, in most strains of mice studied, Ly-49G2(+) NK cells m ust also be eliminated. The putative roles of these NK cell subsets in clin ical transplantation remains to be elucidated. (C) 2000 by The American Soc iety of Hematology.