Blood, Vol. 95 No. 12 (June 15), 2000:
pp. 3840-3844
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
Arati Raziuddin,
Michael Bennett,
Robin Winkler-Pickett,
John R. Ortaldo,
Dan L. Longo, and
William J. Murphy
From the Intramural Research Support Program, SAIC-Frederick,
and the Laboratory of Experimental Immunology, National
Cancer Institute, Frederick Cancer Research and Development Center,
Frederick, MD; the University of Texas Southwestern Medical Center,
Dallas, TX; and the National Institute on Aging, Baltimore, MD.
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 H2b
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, 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.
