TY - JOUR
T1 - Cutting edge
T2 - IL-2 signals determine the degree of TCR signaling necessary to support regulatory T cell proliferation in vivo
AU - Zou, Tao
AU - Satake, Atsushi
AU - Corbo-Rodgers, Evann
AU - Schmidt, Amanda M.
AU - Farrar, Michael A.
AU - Maltzman, Jonathan S.
AU - Kambayashi, Taku
PY - 2012/7/1
Y1 - 2012/7/1
N2 - To ensure immune tolerance, regulatory T cell (Treg) numbers must be maintained by cell division. This process has been thought to be strictly dependent on the Treg TCR interacting with MHC class II. In this study, we report that Treg division does not absolutely require cell-autonomous TCR signaling in vivo, depending on the degree of IL-2-mediated stimulation provided. At steady state IL-2 levels, Tregs require cell-autonomous TCR signaling to divide. However, when given exogenous IL-2 or when STAT5 is selectively activated in Tregs, Treg division can occur independently of MHC class II and TCR signaling. Thus, depending on the amount of IL-2R stimulation, a wide range of TCR signals supports Treg division, which may contribute to preservation of a diverse repertoire of Treg TCR specificities. These findings also have therapeutic implications, as TCR signaling by Tregs may not be required when using IL-2 to increase Treg numbers for treatment of inflammatory disorders.
AB - To ensure immune tolerance, regulatory T cell (Treg) numbers must be maintained by cell division. This process has been thought to be strictly dependent on the Treg TCR interacting with MHC class II. In this study, we report that Treg division does not absolutely require cell-autonomous TCR signaling in vivo, depending on the degree of IL-2-mediated stimulation provided. At steady state IL-2 levels, Tregs require cell-autonomous TCR signaling to divide. However, when given exogenous IL-2 or when STAT5 is selectively activated in Tregs, Treg division can occur independently of MHC class II and TCR signaling. Thus, depending on the amount of IL-2R stimulation, a wide range of TCR signals supports Treg division, which may contribute to preservation of a diverse repertoire of Treg TCR specificities. These findings also have therapeutic implications, as TCR signaling by Tregs may not be required when using IL-2 to increase Treg numbers for treatment of inflammatory disorders.
UR - http://www.scopus.com/inward/record.url?scp=84862856290&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862856290&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1200507
DO - 10.4049/jimmunol.1200507
M3 - Article
C2 - 22623329
AN - SCOPUS:84862856290
SN - 0022-1767
VL - 189
SP - 28
EP - 32
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -