The role of OX40 (CD134) in T-cell memory generation.

Memory T-cell generation is limited by activation-induced cell death during the effector T-cell stage. Cell surface proteins are known to transmit signals that either accentuate or limit T-cell death after activation. This chapter will focus on the TNF-receptor family member OX40, which is expressed on effector T cells and when engaged greatly enhances survival of T cells leading to increased memory T-cell generation. Targeting OX40 in vivo can alter the fate ofT-cell survival. Enhancing OX40 signaling during Ag priming through agonists increases memory T-cell development, while blocking OX40 signaling decreases the memory T-cell pool. These two opposing outcomes provide therapeutic tools for blocking inflammation in autoimmune conditions and enhancing immunity in hosts harboring cancer or chronic pathogens. OX40 agonists and antagonists are in the first stages of human clinical trials and their therapeutic potential will soon be realized.