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Journal of Virology, January 2002, p. 450-454, Vol. 76, No. 1
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.1.450-454.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Essential Roles for CD8+ T Cells and Gamma Interferon in Protection of Mice against Retrovirus-Induced Immunosuppression

Ulf Dittmer,1 Brent Race,2 Karin E. Peterson,2 Ingunn M. Stromnes,2 Ronald J. Messer,2 and Kim J. Hasenkrug2*

Institut für Virologie der Universität Würzburg, Würzburg, Germany,1 Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana2

Received 25 July 2001/ Accepted 24 September 2001

It is known that both animal and human retroviruses typically cause immunosuppression in their respective hosts, but the mechanisms by which this occurs are poorly understood. The present study uses Friend virus (FV) infections of mice as a model to determine how major histocompatibility complex (MHC) genes influence immunosuppression. Previously, MHC-I genes were shown to influence antibody responses to potent antigenic challenges given during acute FV infection. The mapping of an immune response to an MHC-I gene implicated CD8+ T cells in the mechanism, so we directly tested for their role by using in vivo CD8+ T-cell depletions. Mice resistant to FV-induced immunosuppression became susceptible when they were depleted of CD8+ T cells. Resistance also required gamma interferon (IFN-{gamma}), as in vivo neutralization of IFN-{gamma} converted mice from a resistant to susceptible phenotype. On the other hand, susceptibility to FV-induced immunosuppression was dependent on the immunosuppressive cytokine, interleukin-10 (IL-10), as antibody responses were restored in susceptible mice when IL-10 function was blocked in vivo. Thus, FV-induced immunosuppression of antibody responses involves complex mechanisms controlled at least in part by CD8+ T cells.

* Corresponding author. Mailing address: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, 903 S. 4th St., Hamilton, MT 59840. Phone: (406) 363-9310. Fax: (406) 363-9204. E-mail:khasenkrug{at}nih.gov.

Journal of Virology, January 2002, p. 450-454, Vol. 76, No. 1
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.1.450-454.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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