Reduction of retrovirus-induced immunosuppression by in vivo modulation of T cells during acute infection.
Chronic infection with Friend retrovirus is associated with suppressed antitumor immune responses. In the present study we investigated whether modulation of T-cell responses during acute infection would restore antitumor immunity in persistently infected mice. T-cell modulation was done by treatments with DTA-1 anti- glucocorticoid-induced tumor necrosis factor receptor monoclonal antibodies. The DTA-1 monoclonal antibody is nondepleting and delivers costimulatory signals that both enhance the activation of effector T cells and inhibit suppression by regulatory T cells. DTA-1 therapy produced faster Th1 immune responses, significant reductions in both acute virus loads and pathology and, most importantly, long-term improvement of CD8(+) T-cell-mediated antitumor responses.
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Hong
H
He
Ronald J
RJ
Messer
Shimon
S
Sakaguchi
Guojun
G
Yang
Shelly J
SJ
Robertson
Kim J
KJ
Hasenkrug
D000208:Acute Disease; D000818:Animals; D005260:Female; D005622:Friend murine leukemia virus; D053450:Glucocorticoid-Induced TNFR-Related Protein; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors; D012192:Retroviridae Infections / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D019562:Viral Load
D053450:Glucocorticoid-Induced TNFR-Related Protein; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C106544:Tnfrsf18 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma