In vivo ligation of glucocorticoid-induced TNF receptor enhances the T-cell immunity to herpes simplex virus type 1.
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.
The Immunomodulation Research Center and Department of Biological Science, University of Ulsan, Ulsan 680-749, Korea.
Soojin
S
La
Eunhwa
E
Kim
Byungsuk
B
Kwon
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D053450:Glucocorticoid-Induced TNFR-Related Protein; D005938:Glucocorticoids / Q000494:pharmacology*; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000472:pathogenicity; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology
D000911:Antibodies, Monoclonal; D053450:Glucocorticoid-Induced TNFR-Related Protein; D005938:Glucocorticoids; D010446:Peptide Fragments; D015375:Receptors, Interleukin-2; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C106544:Tnfrsf18 protein, mouse; D007371:Interferon-gamma