T cell receptor-mediated activation of CD4⁺CD44^hi T cells bypasses Bcl10: An implication of differential NF-κB dependence of naïve and memory T cells during T cell receptor-mediated responses

Previous studies have demonstrated that Bcl10 (B-cell leukemia/lymphoma 10) is essential for T cell receptor-mediated NF-κB activation and subsequent proliferation and interleukin 2 (IL2) production. However, here we demonstrate that, contrary to expectations, Bcl10 is differentially required for T cell activation, including for both proliferation and cytokine production. When CD4⁺ and CD8⁺ T cells were divided based on expression levels of CD44, which distinguishes naïve cells (CD44^lo) versus those that are antigen-experienced (CD44^hi), IL2 production by and proliferation of CD4⁺CD44^lo naïve cells and both subpopulations of CD8⁺ T cells were clearly Bcl10-dependent, whereas these same functional properties of CD4⁺CD44^hi T cells occurred largely independent of Bcl10. As with the other subpopulations of T cells, CD4⁺CD44^hi T cells did not activate the NF-κB pathway in the absence of Bcl10; nevertheless, these CD4⁺CD44 ^hi antigen-experienced T cells efficiently secreted IL2 after T cell receptor stimulation. Strikingly, therefore, T cell receptor-mediated IL2 production in these cells is NF-κB-independent. Our studies suggest that antigen-experienced CD4⁺ T cells differ from their naïve counterparts and from CD8⁺ T cells in their ability to achieve activation independent of the Bcl10/NF-κB pathway.