Regulation of transforming growth factor-β production by interleukin-12

✍ Scribed by Thomas Marth; Warren Strober; Robert A. Seder; Brian L. Kelsall

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 847 KB
• Volume: 27
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830270524

✦ Synopsis

Regulation of transforming growth factor-p production by interleukin-=

The induction of peripheral tolerance following oral antigen administration in several autoimmune disease and conventional animal models correlates with the production of transforming growth factor-fJ (TGF-p) and T helper type 2 (Th2) cytokines. The factors regulating TGF-P production and its relation to the Th2 response, however, have not been defined. We demonstrate that the systemic administration of antibodies to interleukin (1L)-12 to ovalbumin (0VA)-T cell receptor (TCR) transgenic mice fed high doses of OVA, followed by systemic OVA challenge, substantially enhances TGF-P, but not IL-4 production by peripheral T cells. Furthermore, we demonstrate in an in vitro T cell differentiation model that naive (CD4+/Mel-14hi) OVA-TCR-T cells stimulated with OVApulsed dendritic cells (DC) produce four-to fivefold higher amounts of TGF-P when cultured with anti-IL-12 or anti-interferon-y (IFN-y). In this in vitro system, IL-4 was not required for TGF-P production by T cells; however, it appeared to enhance levels of TGF-P by promoting the growth of TGF-pproducing cells. Our findings demonstrate that IL-12 and IFN-y are important negative regulators of TGF-P production both in vivo and in vitro, and that their modulation may be of benefit for the treatment of autoimmune disorders.

In recent studies TGF-P has been shown to play a role in oral tolerance. Thus, as reviewed by Weiner et al. [12], repeated antigen feeding (particularly at low doses) is associated with the appearance of antigen-specific T cells [I 163931