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Journal of Virology, April 2000, p. 3650-3658, Vol. 74, No. 8
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Bystander Sensitization to Activation-Induced Cell Death as a Mechanism of Virus-Induced Immune Suppression

Christopher C. Zarozinski,dagger James M. McNally, Barbara L. Lohman,Dagger Keith A. Daniels, and Raymond M. Welsh*

Department of Pathology, University of Massachusetts Medical Center, Worcester, Massachusetts 01655

Received 18 October 1999/Accepted 18 January 2000

Viral infections which induce strong T-cell responses are often characterized by a period of transient immunodeficiency associated with the failure of host T cells to proliferate in response to mitogens or to mount memory recall responses to other antigens. During acute infections, most of the activated, proliferating virus-specific T cells are sensitized to undergo apoptosis on strong T-cell receptor (TCR) stimulation, but it has not been known why memory T cells not specific for the virus fail to proliferate on exposure to their cognate antigen. Using a lymphocytic choriomeningitis virus (LCMV) infection model in which LCMV-immune Thy 1.1+ splenocytes are adoptively transferred into Thy 1.2+ LCMV carrier mice, we demonstrate here that T cells clearly defined as not specific for the virus are sensitized to undergo activation-induced cell death on TCR stimulation in vitro. This bystander sensitization was in part dependent on the expression of Fas ligand (FasL) on the activated virus-specific cells and gamma interferon (IFN-gamma ) receptor expression on the bystander T cells. We propose that FasL from highly activated antiviral T cells may sensitize IFN-gamma -conditioned T cells not specific for the virus to undergo apoptosis rather than to proliferate on encountering antigen. This may in part explain the failure of memory T cells to respond to recall antigens during acute and persistent viral infections.

* Corresponding author. Mailing address: Department of Pathology, University of Massachusetts Medical Center, 55 Lake Ave. North, Worcester, MA 01655. Phone: (508) 856-5819. Fax: (508) 856-5780. E-mail: raymond.welsh{at}umassmed.edu.

dagger Present address: Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02155.

Dagger Present address: California Regional Primate Research Center, University of California, Davis, CA 95615.

Journal of Virology, April 2000, p. 3650-3658, Vol. 74, No. 8
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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