TY - JOUR
T1 - Cutting edge
T2 - CD28 and c-Rel-dependent pathways initiate regulatory T cell development
AU - Vang, Kieng B.
AU - Yang, Jianying
AU - Pagán, Antonio J.
AU - Li, Lin Xi
AU - Wang, Junmei
AU - Green, Jonathan M.
AU - Beg, Amer A.
AU - Farrar, Michael A.
PY - 2010/4/15
Y1 - 2010/4/15
N2 - Regulatory T cell (Treg) development proceeds via a two-step process in which naive CD4+ thymocytes are first converted into CD4 +CD25+CD122+GITR+Foxp3- Treg progenitors, followed by a second step in which IL-2 converts these Treg progenitors into CD4+Foxp3+ Tregs. The costimulatory molecule CD28 is required for efficient Treg development. However, the stage at which CD28 affects Treg development remains undefined. In this article, we demonstrate that Cd28-/- mice lack Treg progenitors. Furthermore, the P187YAP motif in the cytoplasmic tail of CD28, which links CD28 to Lck activation, is required for this process. In contrast, the Y 170MNM motif, which links CD28 to PI3K activation, is not required for Treg progenitor development. Finally, the CD28/Lck pathway was shown to activate the NF-κB family of transcription factors. We demonstrate that c-Rel, but not NF-κB1, promotes the development of Treg progenitors. Thus, a CD28/c-Rel-dependent pathway is involved in initiating Treg development.
AB - Regulatory T cell (Treg) development proceeds via a two-step process in which naive CD4+ thymocytes are first converted into CD4 +CD25+CD122+GITR+Foxp3- Treg progenitors, followed by a second step in which IL-2 converts these Treg progenitors into CD4+Foxp3+ Tregs. The costimulatory molecule CD28 is required for efficient Treg development. However, the stage at which CD28 affects Treg development remains undefined. In this article, we demonstrate that Cd28-/- mice lack Treg progenitors. Furthermore, the P187YAP motif in the cytoplasmic tail of CD28, which links CD28 to Lck activation, is required for this process. In contrast, the Y 170MNM motif, which links CD28 to PI3K activation, is not required for Treg progenitor development. Finally, the CD28/Lck pathway was shown to activate the NF-κB family of transcription factors. We demonstrate that c-Rel, but not NF-κB1, promotes the development of Treg progenitors. Thus, a CD28/c-Rel-dependent pathway is involved in initiating Treg development.
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U2 - 10.4049/jimmunol.0903933
DO - 10.4049/jimmunol.0903933
M3 - Article
C2 - 20228198
AN - SCOPUS:77952767221
SN - 0022-1767
VL - 184
SP - 4074
EP - 4077
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -