Characterization of the phenotype and function of CD8(+), alpha / beta(+) NKT cells from tumor-bearing mice that show a natural killer cell activity and lyse multiple tumor targets.
Natural Killer (NK) T cells are a specialized T cell population that co-expresses receptors of the NK lineage with the alpha / beta TCR receptor and other T cell surface markers. Their functions, regulation and relationship to other cells in the immune system are not fully understood. This report demonstrates that tumor-bearing C57BL / 6 mice have a population of NKT cells that co-express CD8 and CD161 (NK1.1) surface markers. These cells are maintained in long-term culture with T helper 2 (Th2) cytokine interleukin-4 (IL-4), but produce large amounts of Th1 cytokine interferon-gamma (IFN-gamma) following activation. NK1.1(+)CD8(+) T cells show a potent NK-like cytotoxic activity against multiple tumor targets, and lysis is independent of major histocompatibility complex (MHC)-class I or non-classical MHC-class I molecules (Qa, TL). The NK1.1(+)CD8(+) T cells express Vbeta14 chain of the TCR. These NKT cells are not CD1d restricted, and their cytotoxic activity is CD1d independent. Therefore, they represent a unique subset of T cells with an unknown restriction element which produce large quantities of IFN-gamma following expansion with IL-4. Furthermore, their cytotoxic activity is enhanced by B7 co-stimulatory molecules present on tumor cells. CD161(+) T cells that are expanded in tumor-bearing hosts may function as a part of the innate immune system with potential role(s) in tumor surveillance.
Stremmel
C
C
Center for Neurological Diseases, Brigham and Womens Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.
Exley
M
M
Balk
S
S
Hohenberger
W
W
Kuchroo
V K
VK
D000818:Animals; D000941:Antigens / Q000032:analysis; D018949:Antigens, CD1 / Q000502:physiology; D055610:Antigens, CD1d; D000950:Antigens, Ly; D000954:Antigens, Surface; D018122:B7-1 Antigen / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D051379:Mice; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B; D009374:Neoplasms, Experimental / Q000276:immunology*; D011506:Proteins / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D018417:Th1 Cells / Q000276:immunology; D014407:Tumor Cells, Cultured
D000941:Antigens; D018949:Antigens, CD1; D055610:Antigens, CD1d; D000950:Antigens, Ly; D000954:Antigens, Surface; D018122:B7-1 Antigen; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015847:Interleukin-4; D007371:Interferon-gamma