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Cutting Edge: IL-2 Immune Complexes As a Therapy for Persistent Virus Infection ¹

Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03748

There is an urgent need to develop novel therapies for controlling recurrent virus infections in immune suppressed patients. Disease associated with persistent -herpesvirus infection (EBV, HHV-8) is a significant problem in AIDS patients and transplant recipients, and clinical management of these conditions is difficult. Disease occurs because of a failure in immune surveillance to control the persistent infection, which arises in AIDS patients principally because of an erosion of the CD4⁺ T cell compartment. Immune surveillance failure followed by -herpesvirus recrudescence can be modeled using murine -herpesvirus in CD4 T cell-depleted mice. We show that enhancement of IL-2 signaling using IL-2/anti-IL-2 immune complexes substantially improves immune surveillance in the context of suppressed immunity and enhances control of the infection. This effect was not due solely to increased numbers of virus-specific CD8 T cells but rather to enhanced cytotoxicity mediated by the perforin-granzyme pathway.

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 Funding was provided in part by National Institutes of Health Grants AI069943, CA103642, and T32AI07363.

² Address correspondence and reprint requests to Dr. Edward J Usherwood, Microbiology and Immunology Department, Borwell Building, One Medical Center Drive, Lebanon, NH 03766. E-mail address: Edward.J.Usherwood{at}dartmouth.edu

³ Abbreviations used in this paper: MHV-68, murine -herpesvirus 68; i.n., intranasal(ly).

⁴ The online version of this article contains supplemental material.