Lineage-specific differences among CD8(+) T cells in their dependence of NF-kappa B/Rel signaling

Whereas most CD8(+) T cells in lymph nodes and spleen express the CD8 alpha beta heterodimer and depend absolutely on thymic competence for their deve lopment, a substantial population of T cells expressing CD8 alpha alpha mat ures extrathymically. Although the existence of these CD8 sublineages is we ll established, relatively little is known about differences that might exi st among CD8 cells in their requirement for particular transcriptional path ways during the development and maintenance of normal populations. Transgen ic mice whose T lineage expresses an I kappa B alpha mutant exhibited decre ased NF-kappa B signaling and a diminution in mature CD8 T cells. We now ha ve determined that although TCR-dependent CD69 induction by CD8 alpha alpha and CD8 alpha beta T cells was unaffected by inhibition of NF-kappa B, TCR alpha beta CD8 alpha beta T cells were preferentially reduced compared to their TCR alpha beta CD8 alpha alpha or TCR gamma delta counterparts. This finding was most prominent in spleen, but was also apparent in Peyer's patc hes of transgenic mice. In addition, diminished antiviral cytotoxic respons es of CD8 alpha beta intraepithelial lymphocytes were observed after enteri c reovirus infection. Taken together, these results indicate that NF-kappa B signaling is more important for the thymus-dependent TCR alpha beta CD8 a lpha beta population than for other CD8 lineages, and thus regulates the nu mber, function, and normal balance of CD8 subsets in the periphery.