TGF-beta: the perpetrator of immune suppression by regulatory T cells and suicidal T cells.

Innate and adaptive immunity function to eliminate foreign invaders and respond to injury while enabling coexistence with commensal microbes and tolerance against self and innocuous agents. Although most often effective in accomplishing these objectives, immunologic processes are not fail-safe and may underserve or be excessive in protecting the host. Checks and balances to maintain control of the immune system are in place and are becoming increasingly appreciated as targets for manipulating immunopathologic responses. One of the most recognized mediators of immune regulation is the cytokine transforming growth factor-beta (TGF-beta), a product of immune and nonimmune cells. Emerging data have unveiled a pivotal role for TGF-beta as a perpetrator of suppression by CD4(+)CD25(+) regulatory T (Treg) cells and in apoptotic sequelae. Through its immunosuppressive prowess, TGF-beta effectively orchestrates resolution of inflammation and control of autoaggressive immune reactions by managing T cell anergy, defining unique populations of Treg cells, regulating T cell death, and influencing the host response to infections.