1887

Abstract

Acute infection with lymphocytic choriomeningitis virus (LCMV) normally results in robust clonal expansion of virus-specific CD8 T cells, which in turn control the primary infection. However, similar infection of myeloid differentiation factor 88 (MyD88)-deficient mice leads to a markedly impaired T-cell response and chronic infection. It has been found previously that impairment of the innate immune response is not sufficient to explain this profound change in outcome. Using adoptive transfer of CD8 T cells, this study demonstrated unequivocally that T-cell expression of MyD88 is critical for a normal T-cell response to LCMV. In addition, it was found that expression of MyD88 is superfluous during early activation and proliferation of the antigen-activated CD8 T cells, but plays a critical role in the sustained expansion of the antigen-specific CD8 T-cell population during the primary T-cell response. Interestingly, a critical role for MyD88 was evident only under conditions of systemic infection with virus capable of causing prolonged infection, suggesting that MyD88 expression may function as an internal regulator of the threshold for antigen-driven, exhaustive differentiation.

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2009-02-01
2019-11-19
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References

  1. Adachi, O., Kawai, T., Takeda, K., Matsumoto, M., Tsutsui, H., Sakagami, M., Nakanishi, K. & Akira, S. ( 1998; ). Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function. Immunity 9, 143–150.[CrossRef]
    [Google Scholar]
  2. Aichele, P., Unsoeld, H., Koschella, M., Schweier, O., Kalinke, U. & Vucikuja, S. ( 2006; ). CD8 T cells specific for lymphocytic choriomeningitis virus require type I IFN receptor for clonal expansion. J Immunol 176, 4525–4529.[CrossRef]
    [Google Scholar]
  3. Akira, S. & Takeda, K. ( 2004; ). Toll-like receptor signalling. Nat Rev Immunol 4, 499–511.[CrossRef]
    [Google Scholar]
  4. Andreasen, S. O., Christensen, J. E., Marker, O. & Thomsen, A. R. ( 2000; ). Role of CD40 ligand and CD28 in induction and maintenance of antiviral CD8+ effector T cell responses. J Immunol 164, 3689–3697.[CrossRef]
    [Google Scholar]
  5. Battegay, M., Cooper, S., Althage, A., Banziger, J., Hengartner, H. & Zinkernagel, R. M. ( 1991; ). Quantification of lymphocytic choriomeningitis virus with an immunological focus assay in 24- or 96-well plates. J Virol Methods 33, 191–198.[CrossRef]
    [Google Scholar]
  6. Christensen, J. E., Wodarz, D., Christensen, J. P. & Thomsen, A. R. ( 2004; ). Perforin and IFN-γ do not significantly regulate the virus-specific CD8+ T cell response in the absence of antiviral effector activity. Eur J Immunol 34, 1389–1394.[CrossRef]
    [Google Scholar]
  7. Cottalorda, A., Verschelde, C., Marcais, A., Tomkowiak, M., Musette, P., Uematsu, S., Akira, S., Marvel, J. & Bonnefoy-Berard, N. ( 2006; ). TLR2 engagement on CD8 T cells lowers the threshold for optimal antigen-induced T cell activation. Eur J Immunol 36, 1684–1693.[CrossRef]
    [Google Scholar]
  8. Gelman, A. E., Zhang, J., Choi, Y. & Turka, L. A. ( 2004; ). Toll-like receptor ligands directly promote activated CD4+ T cell survival. J Immunol 172, 6065–6073.[CrossRef]
    [Google Scholar]
  9. Holst, P. J., Bartholdy, C., Stryhn, A., Thomsen, A. R. & Christensen, J. P. ( 2007; ). Rapid and sustained CD4+ T-cell-independent immunity from adenovirus-encoded vaccine antigens. J Gen Virol 88, 1708–1716.[CrossRef]
    [Google Scholar]
  10. Iwasaki, A. & Medzhitov, R. ( 2004; ). Toll-like receptor control of the adaptive immune responses. Nat Immunol 5, 987–995.[CrossRef]
    [Google Scholar]
  11. Jung, A., Kato, H., Kumagai, Y., Kumar, H., Kawai, T., Takeuchi, O. & Akira, S. ( 2008; ). Lymphocytoid choriomeningitis virus activates plasmacytoid dendritic cells and induces a cytotoxic T-cell response via MyD88. J Virol 82, 196–206.[CrossRef]
    [Google Scholar]
  12. Kolumam, G. A., Thomas, S., Thompson, L. J., Sprent, J. & Murali-Krishna, K. ( 2005; ). Type I interferons act directly on CD8 T cells to allow clonal expansion and memory formation in response to viral infection. J Exp Med 202, 637–650.[CrossRef]
    [Google Scholar]
  13. Kristensen, N. N., Christensen, J. P. & Thomsen, A. R. ( 2002; ). High numbers of IL-2-producing CD8+ T cells during viral infection: correlation with stable memory development. J Gen Virol 83, 2123–2133.
    [Google Scholar]
  14. Lopez, C. B., Yount, J. S. & Moran, T. M. ( 2006; ). Toll-like receptor-independent triggering of dendritic cell maturation by viruses. J Virol 80, 3128–3134.[CrossRef]
    [Google Scholar]
  15. Lord, K. A., Hoffman-Liebermann, B. & Liebermann, D. A. ( 1990; ). Nucleotide sequence and expression of a cDNA encoding MyD88, a novel myeloid differentiation primary response gene induced by IL6. Oncogene 5, 1095–1097.
    [Google Scholar]
  16. Medzhitov, R., Preston-Hurlburt, P., Kopp, E., Stadlen, A., Chen, C., Ghosh, S. & Janeway, C. A., Jr ( 1998; ). MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways. Mol Cell 2, 253–258.[CrossRef]
    [Google Scholar]
  17. Nansen, A., Jensen, T., Christensen, J. P., Andreasen, S. O., Ropke, C., Marker, O. & Thomsen, A. R. ( 1999; ). Compromised virus control and augmented perforin-mediated immunopathology in IFN-γ-deficient mice infected with lymphocytic choriomeningitis virus. J Immunol 163, 6114–6122.
    [Google Scholar]
  18. Rahman, A. H., Cui, W., Larosa, D. F., Taylor, D. K., Zhang, J., Goldstein, D. R., Wherry, E. J., Kaech, S. M. & Turka, L. A. ( 2008; ). MyD88 plays a critical T cell-intrinsic role in supporting CD8 T cell expansion during acute lymphocytic choriomeningitis virus infection. J Immunol 181, 3804–3810.[CrossRef]
    [Google Scholar]
  19. Thoma-Uszynski, S., Stenger, S., Takeuchi, O., Ochoa, M. T., Engele, M., Sieling, P. A., Barnes, P. F., Rollinghoff, M., Bolcskei, P. L. & other authors ( 2001; ). Induction of direct antimicrobial activity through mammalian Toll-like receptors. Science 291, 1544–1547.[CrossRef]
    [Google Scholar]
  20. Thompson, L. J., Kolumam, G. A., Thomas, S. & Murali-Krishna, K. ( 2006; ). Innate inflammatory signals induced by various pathogens differentially dictate the IFN-I dependence of CD8 T cells for clonal expansion and memory formation. J Immunol 177, 1746–1754.[CrossRef]
    [Google Scholar]
  21. Thomsen, A. R., Nansen, A., Andersen, C., Johansen, J., Marker, O. & Christensen, J. P. ( 1997; ). Cooperation of B cells and T cells is required for survival of mice infected with vesicular stomatitis virus. Int Immunol 9, 1757–1766.[CrossRef]
    [Google Scholar]
  22. Wherry, E. J. & Ahmed, R. ( 2004; ). Memory CD8 T-cell differentiation during viral infection. J Virol 78, 5535–5545.[CrossRef]
    [Google Scholar]
  23. Zhou, S., Kurt-Jones, E. A., Mandell, L., Cerny, A., Chan, M., Golenbock, D. T. & Finberg, R. W. ( 2005; ). MyD88 is critical for the development of innate and adaptive immunity during acute lymphocytic choriomeningitis virus infection. Eur J Immunol 35, 822–830.[CrossRef]
    [Google Scholar]
  24. Zhou, S., Kurt-Jones, E. A., Fitzgerald, K. A., Wang, J. P., Cerny, A. M., Chan, M. & Finberg, R. W. ( 2007; ). Role of MyD88 in route-dependent susceptibility to vesicular stomatitis virus infection. J Immunol 178, 5173–5181.[CrossRef]
    [Google Scholar]
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