TGF-beta Activation and Function in Immunity

The cytokine TGF-beta plays an integral role in regulating immune responses. TGF-beta has pleiotropic effects on adaptive immunity, especially in the regulation of effector and regulatory CD4(+) T cell responses. Many immune and nonimmune cells can produce TGF-beta, but it is always produced as an inactive complex that must be activated to exert functional effects. Thus, activation of latent TGF-beta provides a crucial layer of regulation that controls TGF-beta function. In this review, we highlight some of the important functional roles for TGF-beta in immunity, focusing on its context-specific roles in either dampening or promoting T cell responses. We also describe how activation of TGF-beta controls its function in the immune system, with a focus on the key roles for members of the integrin family in this process.