NKT and T cells: coordinate regulation of NK-like phenotype and cytokine production.
A maturation-dependent change in phenotype and cytokine production from relatively immature CD161(-) or CD161(+), IL-13(+)IL-4(+), IFN-gamma(-), to mature CD161(+)CD56(+) IFN-gamma(+) cells occurs in primary human alpha-galactosyl ceramide-reactive CD1d-restricted natural killer T (NKT) cells under the control of IL-12 and other monokines. Modulation of this process upon alpha-galactosyl ceramide stimulation explains the opposite roles of NKT cells to drive type 1 and type 2 immune responses. Because the same developmental changes occurred and were similarly regulated in T cells, the data establish that NKT cells should no longer be considered a functionally unique regulatory subset. However, the results of their analysis can be taken as a model for immunotherapeutic approaches with T cells for which a nominal or surrogate antigen is defined.
Loza
Matthew J
MJ
Jefferson Medical College, Kimmel Cancer Center, Department of Microbiology and Immunology, Philadelphia, PA, USA.
Metelitsa
Leonid S
LS
Perussia
Bice
B
D000328:Adult; D018949:Antigens, CD1 / Q000378:metabolism; D055610:Antigens, CD1d; D000954:Antigens, Surface / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D019002:CD56 Antigen / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D005699:Galactosylceramides / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D037181:Lectins, C-Type / Q000378:metabolism; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*
D018949:Antigens, CD1; D055610:Antigens, CD1d; D000954:Antigens, Surface; C526877:CD1D protein, human; D019002:CD56 Antigen; D016207:Cytokines; D005699:Galactosylceramides; D018793:Interleukin-13; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D015847:Interleukin-4; D007371:Interferon-gamma