Manipulation of regulatory T-cell number and function with CD28-specific monoclonal antibodies.

Suppressor or "regulatory" CD4 T cells play a key role in the control of autoimmunity and overshooting immune responses to foreign antigens, but can also obstruct effective anticancer therapies. The homeostasis and activation of these regulatory T cells (Treg cells) is tightly connected to that of effector CD4 T cells via the costimulatory receptor CD28 and the cytokine IL-2: Both subsets require costimulation to be activated by antigen, and Treg cells additionally depend on IL-2 produced by effector CD4 T cells in a costimulation-dependent fashion. Depending on the therapeutic aim, blockade, or stimulation of CD28 with monoclonal antibodies (mAb) can therefore profoundly affect the size and activity of the Treg compartment. In this chapter, experiments performed in rodents with distinct types of CD28-specific mAb, and the recent failure to translate CD28-driven Treg activation into humans, are discussed.