Open AccessAntigen-Specific Suppression and Immunological Synapse Formation by Regulatory T Cells Require the Mst1 Kinase
Author(s) -
Takashi Tomiyama,
Y. Ueda,
Tomoya Katakai,
Naoyuki Kondo,
Kazuichi Okazaki,
Tatsuo Kinashi
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0073874
Subject(s) - immunological synapse , microbiology and biotechnology , antigen , synapse , biology , kinase , immune system , immunology , chemistry , t cell receptor , t cell , neuroscience
Although the cell-to-cell contact between CD4 + Foxp3 + regulatory T (Treg) and their target cells is important for the suppressor function of Treg cells, the regulation of this process is not well understood. Here we show that the Mst1 kinase plays a critical role in the suppressor function of Treg cells through regulation of cell contact dependent processes. Mst1 -/- Treg cells failed to prevent the development of experimental colitis and antigen-specific suppression of naïve T cells proliferation in vitro . Mst1 -/- Treg cells exhibited defective interactions with antigen-presenting dendritic cells (DCs), resulting in reduced down-regulation of costimulatory molecules. While wild-type CD4 + Foxp3 + Treg cells formed mobile immunological synapses on supported planar membrane, Mst1 -/- Treg cells did not exhibit ICAM-1 ring or central peptide-MHC clustering. Using two-photon imaging we showed that antigen-specific wild-type Treg cells exhibited dynamic mobile contacts with antigen-pulsed DCs bearing stably associated naïve T cells. In contrast, Mst1 -/- Treg had impairments in their interactions with DCs. Thus, Mst1 is required for Treg cells to mediate contact-dependent suppressor functions.