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Journal of Virology, November 2004, p. 11641-11647, Vol. 78, No. 21
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.21.11641-11647.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Reduction of Retrovirus-Induced Immunosuppression by In Vivo Modulation of T Cells during Acute Infection

Hong He,1,{dagger} Ronald J. Messer,1 Shimon Sakaguchi,2 Guojun Yang,1,{ddagger} Shelly J. Robertson,1 and Kim J. Hasenkrug1*

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana,1 Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan2

Received 3 March 2004/ Accepted 21 June 2004

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.

* Corresponding author. Mailing address: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840. Phone: (406) 363-9310. Fax: (406) 363-9286. E-mail: khasenkrug{at}nih.gov.

{dagger} Present address: Laboratory of Immunological Monitoring, Robert W. Franz Cancer Research Center, Providence Portland Medical Center, Portland, OR 97213-2967.

{ddagger} Present address: Laboratory of Cancer Immunobiology, Robert W. Franz Cancer Research Center, Providence Portland Medical Center, Portland, OR 97213-2967.

Journal of Virology, November 2004, p. 11641-11647, Vol. 78, No. 21
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.21.11641-11647.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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