CD28 is Not Required for T cell Activation

It has been almost four decades since CD28 was identified as a major player (co-stimulator) of T cell activation and has been recognized as one of the major milestones in the T cell field. However, the exact underlying mechanism involved in the activation of CD28 still remains poorly understood. Most importantly, the depletion of CD28 in mice did not lead to a major defect in T cell activation response, even when combined with the deletion of ICOS, a homolog of CD28. Here, we propose that CD28 is just a survival receptor, which works together with CD45 to maintain T cell survival. It does not participate in the activation of the T-cell activation process by antigen-presenting cells (APCs) in vivo. Furthermore, we propose that CD28 acts like CD4/CD8 to recruit LCK to activate the PI3 kinase pathway.