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Murine -Herpesvirus 68 Limits Naturally Occurring CD4⁺CD25⁺ T Regulatory Cell Activity following Infection¹

Department of Biology, University of North Carolina, Charlotte, NC 28223

During microbial infections, naturally occurring CD4⁺CD25⁺ T regulatory cells can suppress protective host responses or they can limit pathogen-induced inflammatory responses. The particular role played by these cells seems to depend upon the infectious agent being investigated. -Herpesviruses are efficacious pathogens which are well-known for their ability to induce lymphoproliferative disease and to establish latency in the host. However, no studies have investigated the importance of naturally occurring CD4⁺CD25⁺ T regulatory cells during infection with these viruses. Using the murine model of -herpesvirus infection, murine -herpesvirus 68 (HV-68), we were surprised to find that levels of the CD4⁺CD25⁺ T regulatory cell transcript, FoxP3, continued to decrease as viral latency increased and as the leukocytosis phase of the disease progressed. Consistent with these results, the decrease in FoxP3 protein expression followed similar kinetics. Along with the reduced expression of this regulatory T cell marker, we also observed diminished CD4⁺CD25⁺ T regulatory cell activity in these cells isolated from HV-68-infected animals. Dendritic cells infected in vitro with HV-68 did not alter the ability of normal CD4⁺CD25⁺ regulatory T cells to limit the proliferation of CD4⁺ Th cells following stimulation. Taken together, these studies demonstrate a decreased presence and activity of CD4⁺CD25⁺ T regulatory cells during the mononucleosis-like phase of this viral infection. These alterations in naturally occurring T regulatory cell function may help to explain the dysregulation of the host’s immune response which allows the uncontrolled expansion of leukocytes as viral latency is established.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grant AI32976.

² Address correspondence and reprint requests to Dr. Kenneth L. Bost, Department of Biology, University of North Carolina, 9201 University City Boulevard, Charlotte, NC 28223. E-mail address: klbost{at}email.uncc.edu

³ Abbreviations used in this paper: HV-68, murine -herpesvirus 68; Cp, crossing point.

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