A cell-intrinsic requirement for NF-κB-inducing kinase in CD4 and CD8 T cell memory

Alexander M. Rowe, Susan Murray, Hans Peter Raué, Yoshinobu Koguchi, Mark K. Slifka, David Parker

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    32 Scopus citations


    NF-κB-inducing kinase [(NIK), MAP3K14] is an essential kinase linking a subset of TNFR family members to the noncanonical NF-κB pathway. To assess the cell-intrinsic role of NIK in murine T cell function, we generated mixed bone marrow chimeras using bone marrow from NIK knockout (KO) and wild-type (WT) donor mice and infected the chimeras with lymphocytic choriomeningitis virus (LCMV). The chimeras possess an apparently normal immune system, including a mixture of NIK KO and WT T cells, and the virus was cleared normally. Comparison of the NIK KO and WT CD4 and CD8 T cell responses at 8 d post infection revealed modest but significant differences in the acute response. In both CD4 and CD8 compartments, relatively fewer activated (CD44hi) NIK KO T cells were present, but within the CD44 hi population, a comparable percentage of the activated cells produced IFN-γ in response to ex vivo stimulation with antigenic LCMV peptides, although IL-7R expression was reduced in the NIK KO CD8 T cells. Assessment of the LCMV-specific memory at 65 d post infection revealed many more LCMV-specific WT memory T cells than NIK KO memory T cells in both the CD4 and the CD8 compartments, although the small number of surviving NIK KO memory T cells responded to secondary challenge with virus. These results demonstrate a cellintrinsic requirement for NIK in the generation and/or maintenance of memory T cells in response to acute viral infection.

    Original languageEnglish (US)
    Pages (from-to)3663-3672
    Number of pages10
    JournalJournal of Immunology
    Issue number7
    StatePublished - Oct 1 2013

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology


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