Significant involvement of nuclear factor‐κB‐inducing kinase in proper differentiation of αβ and γδ T cells

Summary Nuclear factor‐κB‐inducing kinase ( NIK ) is known to play a critical role in maintaining proper immune function. This is exemplified in the spontaneous mutant mouse lacking functional NIK , alymphoplasia ( aly ), which is simultaneously immune‐compromised and autoimmune‐prone. To investigate the role of NIK in αβ T‐cell repertoire formation, we analysed T‐cell development in aly / aly mice bearing a transgenic T ‐cell receptor ( TCR ). Although there were no apparent abnormalities in the mature αβ T cells of non‐transgenic aly / aly mice, the maturation efficiency of idiotype high+ T cells in the TCR ‐transgenic mice was lower in aly / aly mice compared with those found in aly /+ mice, suggesting that the mature αβ T‐cell repertoire could be altered by the absence of functional NIK . In one strain of TCR ‐transgenic aly / aly mice with a negatively selecting H‐2 background, the proportion of CD 8 low+ idiotype high+ cells, which are thought to potentially represent the γδ lineage of T cells, was markedly decreased. When the γδ T cells in non‐transgenic aly / aly mice were investigated, the proportion of γδ T cells in the peripheral organs of aly / aly mice was found to be one‐half to one‐fifth of those in aly /+ mice. Analyses of bone marrow chimera mice indicated that NIK in host cells, rather than in donor cells was important for generating a normal number of peripheral γδ T cells. Collectively, these results suggest that NIK could be involved in thymic positive selection of some αβ T cells and that NIK in non‐haematopoietic cells is important for the optimal development and/or maintenance of γδ T cells.