Antigen-specific Treg impair CD8(+) T-cell priming by blocking early T-cell expansion

作者：Chappert Pascal; Leboeuf Marylene; Rameau Philippe; Lalfer Melanie; De**ois Sabine; Liblau Roland S; Danos Olivier; Davoust Jean M; Gross David Alexandre^*

来源：European Journal of Immunology, 2010, 40(2): 339-350.

DOI：10.1002/eji.200839107

• CTL
• Foxp3
• Gene transfer
• Tolerance

Foxp3(+) Treg are crucial for the maintenance of self-tolerance and have been shown to control CD8(+) T-cell effector functions. In addition, Treg are thought to control the priming of CD8(+) T cells, which recognize the same antigens as Treg. Taking advantage of our model of peripheral tolerance induction to influenza hemagglutinin (HA) after HA gene transfer, we found that HA-specific Treg suppress antigen-linked CTL responses through early blockade of CD8(+) T-cell expansion. Confronted with their cognate antigen, Treg expand more rapidly than CD8(+) T cells and are highly suppressive only during the initial stages of immune priming. They nullify HA-specific CD8(+) T-cell responses, local inflammatory responses and rejection of HA transduced cells. When HA gene transfer is performed with extensive tissue inflammation, HA-specific Treg are less effective but still reduce the frequency of newly primed HA-specific CD8(+) T cells and the ensuing frequency of memory CD8(+) T cells. Our results demonstrate that Treg control CTL priming in an antigen-specific manner at the level of T-cell expansion, highlighting how self-reactive Treg could prevent the induction of autoimmune responses through selective blockade of autoreactive T-cell proliferation.

• 出版日期2010-2