Exp Mol Med.  2005 Jun;37(3):193-198.

In vivo ligation of glucocorticoid-induced TNF receptor enhances the T-cell immunity to herpes simplex virus type 1

• La S
• Kim E
• Kwon B

Abstract

GITR (glucocorticoid-induced TNF receptor) is a recently identified member of the TNF receptor superfamily. The receptor is preferentially expressed on CD4+CD25+ regulatory T cells and GITR signals break the suppressive activity of the subset. In this study, we wanted to reveal the in vivo function of GITR in herpes simplex virus type 1 (HSV-1) infection. A single injection of anti-GITR mAb (DTA-1) immediately after viral infection significantly increased the number of CD4+ and CD8+ T cells expressing CD25, an activation surface marker, and secreting IFN-gamma. We confirmed these in vivo observations by showing ex vivo that re-stimulation of CD4+ or CD8+ T cells with a CD4+ or CD8+ T-cell-specific HSV-1 peptide, respectively, induced a significant elevation in cell proliferation and in IFN-gamma secretion. Our results indicate that GITR signals play a critical role in the T-cell immunity to HSV-1.

Keyword

GITR; HSV-1; gB; gD; Th1 cell; CTL

MeSH Terms

Animals
Antibodies, Monoclonal/pharmacology
CD4-Positive T-Lymphocytes/immunology
CD8-Positive T-Lymphocytes/immunology
Cell Proliferation
Female
Glucocorticoids/*pharmacology
Herpes Simplex/*immunology
Herpesvirus 1, Human/pathogenicity
*Immunity, Cellular
Interferon Type II/secretion
*Lymphocyte Activation
Mice
Mice, Inbred BALB C
Peptide Fragments/metabolism
Receptors, Interleukin-2/metabolism
Receptors, Nerve Growth Factor/genetics/immunology/*metabolism
Receptors, Tumor Necrosis Factor/genetics/immunology/*metabolism
Research Support, Non-U.S. Gov't
T-Lymphocytes/*immunology/metabolism/virology