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Journal of Virology, January 2005, p. 202-213, Vol. 79, No. 1
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.1.202-213.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Role of Tumor Necrosis Factor Receptors in Regulating CD8 T-Cell Responses during Acute Lymphocytic Choriomeningitis Virus Infection

M. Suresh,* Anju Singh, and Christopher Fischer

Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin

Received 20 May 2004/ Accepted 23 August 2004

The role of tumor necrosis factor (TNF) in regulating various phases of the antiviral T-cell response is incompletely understood. Additionally, despite strong evidence ascribing a role for TNF in protecting against T-cell-dependent autoimmunity, the underlying mechanisms are still obscure. To address these issues, we have investigated the role of tumor necrosis factor receptors (TNFRs) I (p55R) and II (p75R) in regulating CD8 T-cell responses to lymphocytic choriomeningitis virus (LCMV) with wild-type, p55R-deficient (p55–/–), p75R-deficient (p75–/–), and p55R- and p75R-deficient (DKO) mice. Loss of p55R increased the number of memory CD8 T cells to only one of the two immunodominant epitopes, and p75R deficiency had a minimal impact on the T-cell response to LCMV. Strikingly, deficiency of both p55R and p75R had a more dramatic effect on the LCMV-specific CD8 T-cell response; in the DKO mice, as a sequel to enhanced expansion and a reduction in contraction of CD8 T cells, there was a substantial increase in the number of memory CD8 T cells (specific to the two immunodominant epitopes). While the majority of LCMV-specific memory CD8 T cells in wild-type mice were CD62Lhi CCR7hi (central memory), a major proportion of memory CD8 T cells in DKO mice were CD62Llo CCR7hi. TNFR deficiency did not affect the proliferative renewal of memory CD8 T cells. Taken together, these data suggested that TNFRs p55R and p75R have overlapping roles in downregulating CD8 T-cell responses and establishment of immune homeostasis during an acute viral infection.

* Corresponding author. Mailing address: Dept. of Pathobiological Sciences, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706. Phone: (608) 265-9791. Fax: (608) 263-0438. E-mail: sureshm{at}svm.vetmed.wisc.edu.

Journal of Virology, January 2005, p. 202-213, Vol. 79, No. 1
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.1.202-213.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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