Human V gamma 2V delta 2 T cells produce IFN-gamma and TNF-alpha with an on/off/on cycling pattern in response to live bacterial products.
Whereas cytokine production in alphabeta T cells is rapidly regulated by exposure to peptide Ag, the mechanisms regulating cytokine production by gammadelta T cells are unknown. In this study, we demonstrate that human Vgamma2Vdelta2 T cells produce IFN-gamma and TNF-alpha as early as 2 h after Ag exposure, and that they produce these cytokines in a dose- and time- dependent manner in response to stimulation with a live bacterial product, iso-butylamine (IBA), but not to dead bacteria or LPS. gammadelta T cells began, ceased, and then resumed IFN-gamma and TNF-alpha generation in an on/off/on cycling pattern, both in vitro and in vivo, depending on the presence or absence of IBA. IFN-gamma and TNF-alpha, whose optimum production was dependent on IBA-stimulated gammadelta T cells, were critical for monocyte-mediated killing of Escherichia coli. By limiting cytokine production to periods of direct contact with live bacteria, gammadelta T cells focus their resources at the site of infection, while limiting systemic immunopathology. Thus, human gammadelta T cells may mediate innate resistance to extracellular bacteria via tightly regulated cytokine production without necessarily expanding in number.
Wang
L
L
Lymphocyte Biology Section, Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Das
H
H
Kamath
A
A
Bukowski
J F
JF
D000818:Animals; D000942:Antigens, Bacterial / Q000494:pharmacology*; D001770:Blood Bactericidal Activity / Q000276:immunology; D002082:Butylamines / Q000276:immunology* / Q000494:pharmacology; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D004926:Escherichia coli / Q000254:growth & development / Q000276:immunology; D005110:Extracellular Space / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009000:Monocytes / Q000276:immunology; D020613:Morganella morganii / Q000254:growth & development / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000502:physiology
D000942:Antigens, Bacterial; D002082:Butylamines; D008070:Lipopolysaccharides; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; C053521:isobutylamine; D007371:Interferon-gamma