Differential effects of the rejection of bone marrow allografts by the depletion of activating versus inhibiting Ly-49 natural killer cell subsets.
Natural killer cells mediate the specific rejection of bone marrow cell (BMC) allografts in lethally irradiated mice. The Ly-49 family of molecules present on subsets of murine NK cells appears capable of binding class I MHC molecules, resulting in transmission of an inhibitory signal to the NK cell. These Ly-49 family members have been shown to have an immunoreceptor tyrosine-based inhibitory motif that is responsible for the inhibitory signal. However, a new Ly-49 family member was found that lacks this motif, Ly-49D, and evidence suggests that this may be an activating receptor. We therefore compared the role of the activating Ly-49 member with NK cells bearing inhibitory Ly-49 receptors in BMC rejection. Depletion of Ly-49D+ NK cells in H-2b mice abrogated their ability to reject H-2d BMC allografts. Similarly, Ly-49C+ NK cells also were shown to mediate the specific rejection of H-2d BMC. When both subsets were depleted, an additive enhancement of BMC engraftment was observed, indicating that both subsets play a role in the rejection of allogeneic H-2-homozygous H-2d BMC. However, rejection of H-2(b x d) or D8 (H-2b, Dd transgene) BMC allografts was unaffected by Ly-49C+ NK cell depletion in H-2b mice. In marked contrast, depletion of Ly-49D+ NK cells in H-2b mice totally abrogated the rejection of H-2(b x d) heterozygous BMC in support of in vitro data suggesting that Ly-49D+ NK cells receive activating signals. Therefore, NK subsets demonstrate a differential ability to reject H-2 homozygous and heterozygous BMC.
Raziuddin
A
A
Intramural Research Support Program, SAIC-Frederick, NCI-Frederick Cancer Research and Development Center, MD 21702, USA.
Longo
D L
DL
Mason
L
L
Ortaldo
J R
JR
Bennett
M
M
Murphy
W J
WJ
D000818:Animals; D000950:Antigens, Ly; D016026:Bone Marrow Transplantation / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D006579:Heterozygote; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000276:immunology*; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D055630:Receptors, NK Cell Lectin-Like; D013154:Spleen / Q000166:cytology
D000950:Antigens, Ly; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055630:Receptors, NK Cell Lectin-Like