CD28 costimulation: walking the immunological tightrope.

CD28 function has typically been associated with the generation of effector T-cell responses to Ag. However, it is also clear that CD28 plays an important role in Treg-cell biology. Understanding which functions predominate is important when designing therapeutic interventions based on CD28 targeting. An article by Hünig and colleagues [Eur. J. Immunol. 2013. 43: 188-193] in this issue of the European Journal of Immunology uses an inducible gene deletion approach to reveal that, in the steady state, Treg cells intrinsically require CD28 signals for their maintenance in the periphery, whereas homeostasis of conventional T cells is relatively unaffected. Here we highlight the delicate balance created by the ability of CD28 to modulate both regulatory and effector T-cell responses.