Competition and cooperation: Signal transduction by CD28 and CTLA-4

The closely related members of the Ig-family of co-stimulators CD28 and CTLA-4 (CD152) show distinct functions regarding T cell activation but have also many features in common during T cell differentiation. Although CD28 and CTLA-4 share some of their intracellular binding partners, CD28 is the main activating co-stimulator of T cells while the role of CTLA-4 is to mainly down regulate T cell responses. Despite the well known function of CTLA-4 as a negative regulator of T cell function, new data suggest that CTLA-4 is also able to transmit positive signals for increased survival and might be involved in the generation of the memory compartment. The knowledge of how both molecules transmit their respective signals and how these signals are integrated during a T cell response is of importance for the understanding of T cell mediated immune responses and future therapeutic interventions in immune pathologies.