Requirement for natural killer cells in the induction of cytotoxic T cells.
Cell-mediated immunity involves the participation of both regulatory and cytotoxic cells. The conversion of precursors to effector CD8+ cytotoxic T (Tc) cells requires cell-cell collaboration in which CD4+ T cells are traditionally viewed as helper cells. An in vitro system was used here to demonstrate that the generation of human alloantigen-specific CD8+ Tc cells requires the participation of CD3-CD16+CD56+ NK cells but not CD4+ T helper cells. Depletion of NK cells from responders abolished the induction of alloantigen-specific Tc cells in mixed lymphocyte cultures (MLC). Purified CD5+CD8+ T cells stimulated with alloantigen proliferated but did not differentiate into fully functional effector Tc cells. Coculture of responder CD5+CD8+ T cells with NK cells promoted the conversion of CD8+ Tc cell precursors (pTc) into effector Tc cells. Anti-CD56 mAbs blocked Tc cell induction in MLC, suggesting a role for CD56 molecules expressed on NK cells in either alloantigen recognition or delivery of accessory signals to pTc cells. These findings suggest a novel critical link between the natural and specific immune responses.
Kos
F J
FJ
Department of Pathology, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Engleman
E G
EG
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000276:immunology; D019002:CD56 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D000939:Epitopes; D005805:Genes, MHC Class I / Q000235:genetics; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D007694:Killer Cells, Natural / Q000737:chemistry / Q000502:physiology*; D007959:Lymphocyte Culture Test, Mixed; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D019002:CD56 Antigen; D000939:Epitopes; D007519:Isoantigens