Synergistic OX40 and CD30 signals sustain CD8+ T cells during antigenic challenge

AbstractPrior to acquiring a memory phenotype, antigen‐activated CD8+ T cells need to expand and then undergo a contraction phase. Utilizing two different antigenic stimuli, we provide evidence that the tumor necrosis factor receptors OX40 and CD30 integrate synergistic signals during the expansion phase to help maintain CD8+ effectors. Thus, double deficiency in OX40 and CD30 leads to CD8+ cell loss during expansion after immunization either with OVA or with murine CMV. Following their contraction, OX40‐ and CD30‐deficient CD8+ T cells persist normally in CMV‐infected mice. In contrast, persistence after OVA challenge is dependent on OX40 and CD30. Collectively, our data define the important role of both OX40 and CD30 during CD8+ T‐cell activation, and show that long‐term CD8 persistence after contraction is regulated not only by stimulatory receptors but also by the nature of the antigen or how the antigen is presented.