Elimination in vivo of developing T cells by natural killer cells.
Natural killer cells gauge the absence of self class I MHC on susceptible target cells by means of inhibitory receptors such as members of the Ly49 family. To initiate killing by natural killer cells, a lack of inhibitory signals must be accompanied by the presence of activating ligands on the target cell. Although natural killer cell-mediated rejection of class I MHC-deficient bone marrow (BM) grafts is a matter of record, little is known about the targeting in vivo of specific cellular subsets by natural killer cells. We show here that development of class I MHC-negative thymocytes is delayed as a result of natural killer cell toxicity after grafting of a class I MHC-positive host with class I MHC-negative BM. Double positive thymocytes that persist in the presence of natural killer cells display an unusual T cell receptor-deficient phenotype, yet nevertheless give rise to single positive thymocytes and yield mature class I MHC-deficient lymphocytes that accumulate in the class I MHC-positive host. The resulting class I MHC-deficient CD8 T cells are functional and upon activation remain susceptible to natural killer cell toxicity in vivo. Reconstitution of class I MHC-deficient BM precursors with H2-K(b) by retroviral transduction fully restores normal thymic development.
Department of Pathology, Harvard Medical School, 200 Longwood Ave., Boston, MA 02115, USA.
Eckart
E
Schott
Roberto
R
Bonasio
Hidde L
HL
Ploegh
D000818:Animals; D016026:Bone Marrow Transplantation; D018414:CD8-Positive T-Lymphocytes; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000276:immunology*; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000637:transplantation
D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I