Demonstration of MHC class I-specific cytolytic activity in IL-2-activated NK1+CD3+ cells and evidence of usage of T and NK cell receptors.
Lethally irradiated F1 hybrid mice are able to reject allogeneic or parental marrow within hours of transplantation. It has been shown in several mouse strains that the effector cells responsible for this rejection are NK1+ CD3+, leading to the postulate that NK1 CD3 cells express specific cytolytic activity. Previous attempts to demonstrate this were unsuccessful, however. Here we report that the majority of splenic NK1 CD3 cells is in a nonactivated state and that culture in IL-2 induces specific cytolytic activity. Using unseparated as well as purified cells, we demonstrate that NK1 CD3 cells use the TCR alpha/beta for recognition of MHC class I domains alpha 1 and alpha 2. Cytotoxic specificity matches that of specificity of marrow graft rejection when lymphoblast targets are used. Assay of effector cells on L or tumor cell targets results in nonspecific lysis. The possibility that these targets are recognized via receptors other than TCR is supported by the observation that lysis is inhibited by anti-NK1 antibody. We also show that anti-NK1 is able to induce target lysis in a redirected lysis assay not only in NK1+ CD3- but also NK1+ CD3+ effector cells. The conclusion is drawn that, NK1+ CD3+ cells may utilize two receptors--i.e., NK1 and TCR/CD3.
Takeda
K
K
Department of Microbiology, Norris Comprehensive Cancer Center, University of Southern California School of Medicine, Los Angeles 90033.
Dennert
G
G
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*; D013154:Spleen / Q000276:immunology
D017252:CD3 Complex; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; C489917:Nktr protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011971:Receptors, Immunologic