Low dose TGF-beta attenuates IL-12 responsiveness in murine Th cells

Area of Science:

• Immunology
• Cellular Immunology
• T cell differentiation

Background:

• Interleukin-12 receptor (IL-12R) expression is critical for T helper 1 (Th1) cell development.
• BALB/c CD4+ T cells lose IL-12R beta 2 subunit expression and IL-12 responsiveness upon antigen stimulation under neutral conditions, unlike B10.D2 or F1 T cells.

Purpose of the Study:

• To investigate the role of endogenous transforming growth factor-beta (TGF-β) in the loss of IL-12 responsiveness in BALB/c T cells.
• To elucidate the mechanism by which TGF-β influences Th1/Th2 cell development.

Main Methods:

• Stimulation of DO11.10 CD4+ T cells from different mouse strains (BALB/c, B10.D2, F1) with antigen under varying conditions.
• Use of anti-TGF-β antibodies and exogenous TGF-β to modulate T cell responses.
• Assessment of IL-12R beta 2 subunit expression (mRNA and protein), IL-12 responsiveness, and nitric oxide production.

Main Results:

• Loss of IL-12 responsiveness in BALB/c T cells is mediated by endogenous TGF-β.
• Blocking TGF-β with anti-TGF-β antibodies restores IL-12 responsiveness, IL-12R beta 2 mRNA expression, and nitric oxide production in BALB/c T cells.
• Exogenous TGF-β inhibits the development of IL-12 responsiveness in B10.D2 and F1 T cells.

Conclusions:

• TGF-β plays a significant role in attenuating IL-12R beta 2 expression, thereby inhibiting Th1 cell development.
• The effects of anti-TGF-β are dependent on endogenous interferon-gamma (IFN-γ) and are inhibited by interleukin-4 (IL-4).
• TGF-β acts as a key regulator in directing Th1/Th2 cell fate decisions.