| First Author | Rowe AM | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 7 | Pages | 3663-72 |
| PubMed ID | 24006459 | Mgi Jnum | J:205944 |
| Mgi Id | MGI:5547456 | Doi | 10.4049/jimmunol.1301328 |
| Citation | Rowe AM, et al. (2013) A cell-intrinsic requirement for NF-kappaB-inducing kinase in CD4 and CD8 T cell memory. J Immunol 191(7):3663-72 |
| abstractText | NF-kappaB-inducing kinase [(NIK), MAP3K14] is an essential kinase linking a subset of TNFR family members to the noncanonical NF-kappaB 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-gamma 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. |
