Mast cells are essential intermediaries in regulatory T-cell tolerance

Nature 442, 997-1002 (31 August 2006)

Speaker: 謝家漪                            Time: 13:10~14:00, 11/15/ 2006

Commentator: 黎煥耀 老師                  Place: Room 601

Abstract:

     Naturally arising CD4⁺CD25⁺Foxp3⁺ T_Reg cells (nT_Reg) are derived from the thymus and can be exploited for the prevention autoimmune diseases and induction of immunological tolerance to non-self antigens (such as transplantation tolerance). Mast cells are known to be the primary responders in allergic reactions, but they may also participate to regulate the adaptive immune response in recent studies. Previously, extensive serial analysis of gene expression (SAGE) in tolerant tissue showed that genes predominantly expressed by mast cells were overexpressed in cultures of activated T_Reg cells and in tolerant allograft.⁽¹⁾ These unexpected findings linking mast cells to tolerance prompted to study the potential functional role of mast cells in the establishment of T_Reg-cell-mediated allograft tolerance. First, the authors confirm mast cells related gene up-regulated in tolerant skin allograft by qRT-PCR. Then reconstitute mast cells in mast-cell-deficient mice (W^sh) to suggest an indispensable role for mast cells in survival of skin allograft. Activated TReg cells produce high levels of IL-9 which is mast cell growth factor.⁽²⁾ IL-9 is essential in nT_Reg mediated tolerant allograft in Rag-/- mice reconstitution experiment. nT_Reg cells seem to through the production of IL-9 and other effector molecules to facilitates the accumulation of mast cells in allograft, resulting in the suppression of alloreactive CD8⁺ T cells. ⁽³⁾ These data present a new paradigm by which T_Reg cells might operate and identify a novel role for mast cells in T_Reg-cell-dependent allograft tolerance.

References:

1. Zelenika, D. et al. The role of CD4^＋ T-cell subsets in determining transplantation rejection or tolerance. Immunol. Rev. 182, 164–179 (2001).

2.Zhou, Y. et al. Th2 cytokines and asthma. Interleukin-9 as a therapeutic target for asthma. Respir. Res. 2, 80–84 (2001).

3. Lu, L.-F. et al. Mast cells are essential intermediaries in regulatory T-cell tolerance Nature 442, 997–1002 (2006).