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Blood, 15 October 2002, Vol. 100, No. 8, pp. 3026-3033
TRANSPLANTATION
Increased bone marrow allograft rejection by depletion of NK
cells expressing inhibitory Ly49 NK receptors for donor class I
antigens
Arati Raziuddin,
Dan L. Longo,
Michael Bennett,
Robin Winkler-Pickett,
John R. Ortaldo, and
William J. Murphy
From the Intramural Research Support Program,
SAIC-Frederick and Laboratory of Experimental Immunology, National
Cancer Institute at Frederick, MD; University of Texas Southwestern
Medical Center, Dallas; and National Institute on Aging, Baltimore, MD.
Natural killer (NK) cells are the major effectors of acute
rejection of incompatible bone marrow cell (BMC) grafts in lethally irradiated mice. The immunogenetics of BMC rejection are largely controlled by the coexpression (or not) of inhibitory and stimulatory Ly49 receptors whose ligands are class I major histocompatibility complex (MHC) molecules. The majority of the BMC rejection studies involved low numbers of BMCs that were resisted by host NK cells. In
the present study, larger numbers of BMCs were given in which rejection
was not detected and the role of different Ly49 NK subsets not
presumably involved in the rejection of a particular BMC haplotype was
examined. Surprisingly, the data show that the removal of NK cell
subsets expressing Ly49 inhibitory receptors for donor class I
antigens, which would be predicted to have no effect on the BMC
rejection capability, resulted in the marked rejection of BMCs where no
resistance was normally seen. These results extend the "missing
self" hypothesis to suggest that NK Ly49 inhibitory receptors can
both inhibit activation and killing by those cells, but also can in
some way influence the function of NK cells that do not express that
inhibitory receptor in a cell-cell interaction. This suggests that
caution must be exercised before removal of host NK cell subset is
applied clinically because enhanced BMC rejection may result. Altering
the balance of Ly49 NK subsets may also affect other in vivo activities
of these cells.
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