Human V gamma 2V delta 2 T cells augment migration-inhibitory factor secretion and counteract the inhibitory effect of glucocorticoids on IL-1 beta and TNF-alpha production.
In immune cells, proinflammatory cytokine gene expression is regulated by glucocorticoids, whereas migration-inhibitory factor (MIF), a pleiotropic cytokine, has the unique property of counteracting the inhibitory effect of glucocorticoids on TNF-alpha and IL-1beta secretion. A few lines of evidence suggest that gammadelta T cells play an important role in immunoregulation. However, it is unknown whether human gammadelta T cells participate in regulating MIF secretion, and how gammadelta T cells, glucocorticoids, and cytokines converge to give a unified physiological response. In this study, we demonstrate that human Vgamma2Vdelta2 T cells augment MIF secretion. Remarkably, these Vgamma2Vdelta2 T cells, functioning similarly to MIF in part, counteracted inhibition of dexamethasone on production of IL-1beta and TNF-alpha. SCID mice reconstituted with human PBMC that were mock depleted of Vdelta2 T cells and repeatedly infected with lethal dose of Escherichia coli had shorter survival time than those reconstituted with PBMC that were depleted of Vdelta2 T cells. Thus, human Vgamma2Vdelta2 T cells are likely to play broad-spectrum roles in immunoregulation and immunopathology by influencing MIF secretion and the immunomodulatory function of glucocorticoids.
Wang
Lisheng
L
Lymphocyte Biology Section, Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Das
Hiranmoy
H
Kamath
Arati
A
Li
Lin
L
Bukowski
Jack F
JF
D000818:Animals; D003907:Dexamethasone / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004927:Escherichia coli Infections / Q000209:etiology / Q000276:immunology / Q000401:mortality; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D012772:Shock, Septic / Q000209:etiology / Q000276:immunology / Q000401:mortality; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D007375:Interleukin-1; D008263:Macrophage Migration-Inhibitory Factors; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone