IL-2-activated CD8+CD44high cells express both adaptive and innate immune system receptors and demonstrate specificity for syngeneic tumor cells.
CD8(+) T cells depend on the alphabeta TCR for Ag recognition and function. However, Ag-activated CD8(+) T cells can also express receptors of the innate immune system. In this study, we examined the expression of NK receptors on a population of CD8(+) T cells expressing high levels of CD44 (CD8(+)CD44(high) cells) from normal mice. These cells are distinct from conventional memory CD8(+) T cells and they proliferate and become activated in response to IL 2 via a CD48/CD2-dependent mechanism. Before activation, they express low or undetectable levels of NK receptors but upon activation with IL-2 they expressed significant levels of activating NK receptors including 2B4 and NKG2D. Interestingly, the IL-2-activated cells demonstrate a preference in the killing of syngeneic tumor cells. This killing of syngeneic tumor cells was greatly enhanced by the expression of the NKG2D ligand Rae-1 on the target cell. In contrast to conventional CD8(+) T cells, IL-2-activated CD8(+)CD44(high) cells express DAP12, an adaptor molecule that is normally expressed in activated NK cells. These observations indicate that activated CD8(+)CD44(high) cells express receptors of both the adaptive and innate immune system and may play a unique role in the surveillance of host cells that have been altered by infection or transformation.
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D018801:CD2 Antigens / Q000502:physiology; D000071178:CD48 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis*; D018960:Hyaluronan Receptors / Q000096:biosynthesis*; D007110:Immunity, Active / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D054340:Receptors, KIR; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D018801:CD2 Antigens; D000071178:CD48 Antigen; C000604066:Cd48 protein, mouse; D018984:Epitopes, T-Lymphocyte; D018960:Hyaluronan Receptors; D007376:Interleukin-2; D008565:Membrane Proteins; C491219:Raet1a protein, mouse; D011971:Receptors, Immunologic; D054340:Receptors, KIR