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A cell-intrinsic requirement for NF-κB-inducing kinase in CD4 and CD8 T cell memory.
Rowe, Alexander M; Murray, Susan E; Raué, Hans-Peter; Koguchi, Yoshinobu; Slifka, Mark K; Parker, David C.
Afiliação
  • Rowe AM; Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR 07239.
J Immunol ; 191(7): 3663-72, 2013 Oct 01.
Article em En | MEDLINE | ID: mdl-24006459
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 (CD44(hi)) 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 cell-intrinsic requirement for NIK in the generation and/or maintenance of memory T cells in response to acute viral infection.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T CD4-Positivos / Proteínas Serina-Treonina Quinases / Linfócitos T CD8-Positivos / Memória Imunológica Limite: Animals Idioma: En Ano de publicação: 2013 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T CD4-Positivos / Proteínas Serina-Treonina Quinases / Linfócitos T CD8-Positivos / Memória Imunológica Limite: Animals Idioma: En Ano de publicação: 2013 Tipo de documento: Article