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Journal of Virology, June 2007, p. 6502-6512, Vol. 81, No. 12
0022-538X/07/$08.00+0     doi:10.1128/JVI.00163-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Indirect Regulation of CD4 T-Cell Responses by Tumor Necrosis Factor Receptors in an Acute Viral Infection{triangledown}

Anju Singh,1 Marcel Wüthrich,2 Bruce Klein,2 and M. Suresh1*

Department of Pathobiological Sciences,1 Department of Pediatrics, University of Wisconsin—Madison, Madison, Wisconsin 537062

Received 24 January 2007/ Accepted 20 March 2007

Despite the well-recognized importance of CD4 T-cell help in the induction of antibody production and cytotoxic-T-lymphocyte responses, the regulation of CD4 T-cell responses is not well understood. Using mice deficient for TNF receptor I (TNFR I) and/or TNFR II, we show that TNFR I and TNFR II play redundant roles in down regulating the expansion of CD4 T cells during an acute infection of mice with lymphocytic choriomeningitis virus (LCMV). Adoptive transfer experiments using T-cell-receptor transgenic CD4 T cells and studies with mixed bone marrow chimeras indicated that indirect effects and not direct effects on T cells mediated the suppressive function of TNF on CD4 T-cell expansion during the primary response. Further studies to characterize the indirect effects of TNF suggested a role for TNFRs in LCMV-induced deletion of CD11chi dendritic cells in the spleen, which might be a mechanism to limit the duration of antigenic stimulation and CD4 T-cell expansion. Consequent to enhanced primary expansion, there was a substantial increase in the number of LCMV-specific memory CD4 T cells in the spleens of mice deficient for both TNFR I and TNFR II. In summary, our findings suggest that TNFRs down regulate CD4 T-cell responses during an acute LCMV infection by a non-T-cell autonomous mechanism.

* Corresponding author. Mailing address: Department of Pathobiological Sciences, University of Wisconsin—Madison, 2015 Linden Drive, Madison, WI 53706. Phone: (608) 265-9791. Fax: (608) 263-4715. E-mail: sureshm{at}svm.vetmed.wisc.edu

{triangledown} Published ahead of print on 4 April 2007.

Journal of Virology, June 2007, p. 6502-6512, Vol. 81, No. 12
0022-538X/07/$08.00+0     doi:10.1128/JVI.00163-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hoch, N. E., Guzik, T. J., Chen, W., Deans, T., Maalouf, S. A., Gratze, P., Weyand, C., Harrison, D. G. (2009). Regulation of T-cell function by endogenously produced angiotensin II. Am. J. Physiol. Regul. Integr. Comp. Physiol. 296: R208-R216 [Abstract] [Full Text]  
  • Singh, A., Suresh, M. (2007). A role for TNF in limiting the duration of CTL effector phase and magnitude of CD8 T cell memory. J. Leukoc. Biol. 82: 1201-1211 [Abstract] [Full Text]  


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