TGF‐β: 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 mi- crobes and tolerance against self and innocuous agents. Although most often effective in accom- plishing these objectives, immunologic processes are not fail-safe and may underserve or be exces- sive in protecting the host. Checks and balances to maintain control of the immune system are in place and are becoming increasingly appreciated as tar- gets for manipulating immunopathologic re- sponses. One of the most recognized mediators of immune regulation is the cytokine transforming growth factor- (TGF-), a product of immune and nonimmune cells. Emerging data have unveiled a pivotal role for TGF- as a perpetrator of suppres- sion by CD4CD25 regulatory T (Treg) cells and in apoptotic sequelae. Through its immunosup- pressive prowess, TGF- effectively orchestrates resolution of inflammation and control of autoag- gressive immune reactions by managing T cell an- ergy, defining unique populations of Treg cells, regulating T cell death, and influencing the host response to infections. J. Leukoc. Biol. 76: 000-000; 2004.