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The Journal of Immunology, 2002, 168: 4889-4896.
Copyright © 2002 by The American Association of Immunologists

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} Production1

Lisheng Wang, Hiranmoy Das, Arati Kamath, Lin Li and Jack F. Bukowski2

Lymphocyte Biology Section, Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115

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-1{beta} secretion. A few lines of evidence suggest that {gamma}{delta} T cells play an important role in immunoregulation. However, it is unknown whether human {gamma}{delta} T cells participate in regulating MIF secretion, and how {gamma}{delta} T cells, glucocorticoids, and cytokines converge to give a unified physiological response. In this study, we demonstrate that human V{gamma}2V{delta}2 T cells augment MIF secretion. Remarkably, these V{gamma}2V{delta}2 T cells, functioning similarly to MIF in part, counteracted inhibition of dexamethasone on production of IL-1{beta} and TNF-{alpha}. SCID mice reconstituted with human PBMC that were mock depleted of V{delta}2 T cells and repeatedly infected with lethal dose of Escherichia coli had shorter survival time than those reconstituted with PBMC that were depleted of V{delta}2 T cells. Thus, human V{gamma}2V{delta}2 T cells are likely to play broad-spectrum roles in immunoregulation and immunopathology by influencing MIF secretion and the immunomodulatory function of glucocorticoids.




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[Abstract] [Full Text] [PDF]


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