Transforming growth factor- beta 1, Th1 responses, and autoimmune liver disease

Transforming growth factor- beta 1 (TGF- beta 1) is released during the storage of blood components, particularly platelet concentrates, and transfusion recipients are exposed to high levels of TGF- beta 1. Because TGF- beta 1 is one of the most potent immunosuppressive cytokines known, understanding the immunobiologic functions of TGF- beta 1 may be relevant for understanding the immunobiologic effects of transfusion. Our laboratory studies the biologic effects of TGF- beta 1 in the immune system. Mice deficient in TGF- beta 1 spontaneously develop autoimmunity, confirming the important role of this cytokinean an immune regulator. A few years ago, my laboratory made the observation that genetic background strongly affects the phenotype of TGF- beta 1-/- mice. TGF- beta 1-/- mice on the BALB/c background rapidly develop an aggressive T-cell-mediated hepatitis, whereas TGF- beta 1-/- mice on the 129/CF-1 background do not. In this review, I summarize findings published or in press from our laboratory on disease pathogenesis in TGF- beta 1-/- mice and then discuss some of the exciting (as-yet-unpublished) directions our laboratory is currently taking.