title: NK cells play a critical role in the regulation of class I-deficient hemopoietic stem cell engraftment: evidence for NK tolerance correlates with receptor editing.
abstract: The role that NK cells play in the rejection of hemopoietic stem cell (HSC) and tolerance induction has remained controversial. In this study, we examined whether NK cells play a direct role in the rejection of HSC. Purified HSC from MHC class II-deficient mice engrafted readily in congenic mice, while HSC from class I-deficient donors (beta(2)-microglobulin(-/-) (beta(2)m(-/-))) failed to engraft. Recipient mice lacking CD8(+), CD4(+), or T cells also rejected HSC from class I-deficient donors, pointing directly to NK cells as the effector in rejection of HSC. Recipients, deficient in or depleted of NK cells, engrafted readily with beta(2)m(-/-) HSC. Expression of the activating Ly-49D and inhibitory Ly-49G2 receptors on recipient NK cells was significantly decreased in these beta(2)m(-/-)-->B6 chimeras, and the proportion of donor NK cells expressing Ly-49D was also significantly decreased. Notably, beta(2)m(-/-) chimeras accepted beta(2)m(-/-) HSC in second transplants, demonstrating that NK cells in the chimeras had been tolerized to beta(2)m(-/-). Taken together, our data demonstrate that NK cells play a direct role in the regulation of HSC engraftment, and down-regulation and/or deletion of specific NK subsets in mixed chimeras can contribute to the induction of NK cell tolerance in vivo. Moreover, our data show that bone marrow-derived elements significantly contribute to NK cell development and tolerance.
authors.affiliation: Institute for Cellular Therapeutics, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Huang
authors.forename: Francine
authors.initials: F
authors.lastname: Rezzoug
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: Paula M
authors.initials: PM
authors.lastname: Chilton
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Schanie
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fugier-Vivier
authors.forename: Suzanne T
authors.initials: ST
authors.lastname: Ildstad
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D015395:Histocompatibility Antigens Class I; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000502:physiology*; D037181:Lectins, C-Type / Q000032:analysis; D016131:Lymphocyte Subsets; D051379:Mice; D018345:Mice, Knockout; D055630:Receptors, NK Cell Lectin-Like; D013601:T-Lymphocytes; D001613:beta 2-Microglobulin / Q000172:deficiency*
chemical_list: D000950:Antigens, Ly; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D055630:Receptors, NK Cell Lectin-Like; D001613:beta 2-Microglobulin