Role of natural killer cell subsets in cardiac allograft rejection.
To achieve donor-specific immune tolerance to allogeneic organ transplants, it is imperative to understand the cell types involved in acute allograft rejection. In wild-type mice, CD4(+) T cells are necessary and sufficient for acute rejection of cardiac allografts. However, when T-cell responses are suboptimal, such as in mice treated with costimulation-targeting agents or in CD28-deficient mice, and perhaps in transplanted patients taking immunosuppressive drugs, the participation of other lymphocytes such as CD8(+) T cells and NK1.1(+) cells becomes apparent. We found that host NK but not NKT cells were required for cardiac rejection. Ly49G2(+) NK cells suppressed rejection, whereas a subset of NK cells lacking inhibitory Ly49 receptors for donor MHC class I molecules was sufficient to promote rejection. Notably, rejection was independent of the activating receptors Ly49D and NKG2D. Finally, our experiments supported a mechanism by which NK cells promote expansion and effector function of alloreactive T cells. Thus, therapies aimed at specific subsets of NK cells may facilitate transplantation tolerance in settings of impaired T-cell function.
Department of Pathology, The University of Chicago, Chicago, Illinois, USA.
M E
ME
McNerney
K-M
KM
Lee
P
P
Zhou
L
L
Molinero
M
M
Mashayekhi
D
D
Guzior
H
H
Sattar
S
S
Kuppireddi
C-R
CR
Wang
V
V
Kumar
M-L
ML
Alegre
D000818:Animals; D000950:Antigens, Ly / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005805:Genes, MHC Class I / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016027:Heart Transplantation / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D014184:Transplantation, Homologous
D000950:Antigens, Ly; C527086:Klrk1 protein, mouse; C452844:Ly49G2 receptor; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell