The transforming growth factor beta (TGF-beta) family of proteins are
a set of pleiotropic secreted signaling molecules with unique and pote
nt immunoregulatory properties. TGF-beta 1 is produced by every leukoc
yte lineage, including lymphocytes, macrophages, and dendritic cells,
and its expression serves in both autocrine and paracrine modes to con
trol the differentiation, proliferation, and state of activation of th
ese immune cells. TGF-beta can modulate expression of adhesion molecul
es, provide a chemotactic gradient for leukocytes and other cells part
icipating in an inflammatory response, and inhibit them once they have
become activated. Increased production and activation of latent TGF-b
eta have been linked to immune defects associated with malignancy and
autoimmune disorders, to susceptibility to opportunistic infection, an
d to the fibrotic complications associated with chronic inflammatory c
onditions. In addition to these roles in disease pathogenesis, TGF-bet
a is now established as a principal mediator of oral tolerance and can
be recognized as the sine qua non of a unique subset of effector cell
s that are induced in this process. The accumulated knowledge gained t
hrough extensive in vitro functional analyses and from in vivo animal
models, including newly established TGF-beta gene knockout and transge
nic mice, supports the concept that clinical therapies based on modula
tion of this cytokine represent an important new approach to the treat
ment of disorders of immune function.