title: A cell-intrinsic requirement for NF-κB-inducing kinase in CD4 and CD8 T cell memory.
abstract: 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.
authors.affiliation: Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR 07239.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Rowe
authors.forename: Susan E
authors.initials: SE
authors.lastname: Murray
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Raué
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Koguchi
authors.forename: Mark K
authors.initials: MK
authors.lastname: Slifka
authors.forename: David C
authors.initials: DC
authors.lastname: Parker
mesh_terms: D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D002678:Chimera; D005260:Female; D007156:Immunologic Memory / Q000235:genetics; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D017346:Protein Serine-Threonine Kinases; D020395:Receptors, Interleukin-7; D000097782:NF-kappaB-Inducing Kinase