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Advances in TNF Family Research pp 177–186Cite as

Role of 4-1BBL and TRAF1 in the CD8 T Cell Response to Influenza Virus and HIV

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 691))

Abstract

4-1BB is an inducible member of the TNFR family found on antigen-activated T cells as well as on cells of the innate immune system. 4-1BB is a late-acting survival factor for effector T cells, sustaining CD8 T cell survival in the lung during severe respiratory infection with influenza virus. With milder influenza infections, 4-1BBL is dispensable for initial CD8 T cell responses. However, 4-1BB on the CD8 T cells and 4-1BBL primarily on radioresistant cells are important in maintaining CD8 T cell memory to influenza virus. 4-1BB is induced on memory but not naive CD8 T cells independently of antigen, by common gamma chain cytokines such as IL-15 and IL-2. This allows memory CD8 T cells to respond to 4-1BBL in the absence of antigen. 4-1BB transduces signals via recruitment of TRAF1 and TRAF2. Earlier work had shown that TRAF2 was essential for 4-1BB signaling in T cells, whereas the role of TRAF1 was unclear. Our recent studies have demonstrated the importance of TRAF1 in the survival of activated and memory CD8 T cells. We also showed that 4-1BB and TRAF1 are important in the costimulation-dependent rescue of functional CD8 T cells from a starting population of non-functional HIV-specific T cells isolated from chronically infected individuals. Downstream of 4-1BB, TRAF1 maintains the stability of TRAF2 and allows ERK-dependent depletion of the proapoptotic molecule BIM, resulting in increased CD8 T survival. Recently several reports have identified linkages between autoimmunity and single nucleotide polymorphisms in the TRAF1/C5 region. Further work is required to determine whether specific polymorphisms in TRAF1 could influence the ability of different individuals to respond to infection.

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Acknowledgments

Funding for our research is provided by the Canadian Institutes of Health Research (CIHR) and the Canadian Cancer Society. G.H.Y. Lin is funded by a CIHR studentship; L.M. Snell is funded by the Fonds de la recherche en santé Quebec; C. Wang is funded by an Ontario HIV treatment network studentship; and L. Sabbagh, by a fellowship from the Leukemia and Lymphoma Society of America. T.H.W. holds the sanofi pasteur chair in Human Immunology at the University of Toronto.

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Authors and Affiliations

  1. Department of Immunology, University of Toronto, 1 King’s College Circle, Toronto, M5S 1A8, ON, Canada

    Tania H. Watts, Gloria H.Y. Lin, Chao Wang, Ann J. McPherson, Laura M. Snell & Laurent Sabbagh

  2. Department of Immunology, University of Toronto, Toronto, ON, Canada

    Tania H. Watts

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  1. Tania H. Watts
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  2. Gloria H.Y. Lin
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  4. Ann J. McPherson
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Correspondence to Tania H. Watts .

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Editors and Affiliations

  1. Dept. Biological Chemistry, Weizmann Institute of Science, 1 Herzl Street, Rehovot, 76100, Israel

    David Wallach

  2. Dept. Biological Chemistry, Weizmann Institute of Science, 1 Herzl Street, Rehovot, 76100, Israel

    Andrew Kovalenko

  3. Kennedy Institute of Rheumatology, Imperial College London, Aspenlea Rd. 1, London, W6 8LH, United Kingdom

    Marc Feldmann

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Watts, T.H., Lin, G.H., Wang, C., McPherson, A.J., Snell, L.M., Sabbagh, L. (2011). Role of 4-1BBL and TRAF1 in the CD8 T Cell Response to Influenza Virus and HIV. In: Wallach, D., Kovalenko, A., Feldmann, M. (eds) Advances in TNF Family Research. Advances in Experimental Medicine and Biology, vol 691. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6612-4_19

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