Natural killer (NK) cells are an initial defense against cancers and viruses and can be classified into subsets based on their expression of receptors. These subsets are considered “licensed” if inhibitory receptors are capable of binding host MHC I and “unlicensed” if not. Since in vivo data on licensing and subsets are limited, our studies aim to show licensing in tumor and viral models as well as elucidate the roles of NK subsets in a post-hematopoietic stem cell transplantation (HSCT) setting. We have recently observed that cells bearing the Ly49G2 inhibitory receptor predominated post-HSCT regardless of MHC I haplotype. Additionally, studies in resting mice indicated that the unlicensed subset is the major mediator of murine cytomegalovirus (MCMV) protection. Surprisingly, we have found that depleting unlicensed, Ly49G2+, NK cells from leukemia (C1498) bearing, H2b strain mice after syngeneic HSCT significantly improved survival of mice, while depleting the licensed subset, Ly49C/I+, decreased survival. Furthermore, depletion of the Ly49C/I+ subset resulted in significantly increased viral loads in the liver, spleen, and salivary glands in H2b strain mice infected with MCMV 14 days post-HSCT. Conversely, depletion of the unlicensed ly49G2+ subset resulted in only a minor increase in viral load. Collectively, these data support the importance of NK licensing in tumor and viral models post-HSCT and suggest a regulatory role for the unlicensed subsets.
- Copyright © 2011 by The American Association of Immunologists, Inc.