| First Author | Zhou AX | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 10 | Pages | 5057-64 |
| PubMed ID | 23576681 | Mgi Jnum | J:202565 |
| Mgi Id | MGI:5520022 | Doi | 10.4049/jimmunol.1300065 |
| Citation | Zhou AX, et al. (2013) GARP-TGF-beta complexes negatively regulate regulatory T cell development and maintenance of peripheral CD4+ T cells in vivo. J Immunol 190(10):5057-64 |
| abstractText | The role of surface-bound TGF-beta on regulatory T cells (Tregs) and the mechanisms that mediate its functions are not well defined. We recently identified a cell-surface molecule called Glycoprotein A Repetitions Predominant (GARP), which is expressed specifically on activated Tregs and was found to bind latent TGF-beta and mediate a portion of Treg suppressive activity in vitro. In this article, we address the role of GARP in regulating Treg and conventional T cell development and immune suppression in vivo using a transgenic mouse expressing GARP on all T cells. We found that, despite forced expression of GARP on all T cells, stimulation through the TCR was required for efficient localization of GARP to the cell surface. In addition, IL-2 signals enhanced GARP cell surface expression specifically on Tregs. GARP-transgenic CD4(+) T cells and Tregs, especially those expressing higher levels of GARP, were significantly reduced in the periphery. Mature Tregs, but not conventional CD4(+) T cells, were also reduced in the thymus. CD4(+) T cell reduction was more pronounced within the effector/memory subset, especially as the mouse aged. In addition, GARP-overexpressing CD4(+) T cells stimulated through the TCR displayed reduced proliferative capacity, which was restored by inhibiting TGF-beta signaling. Furthermore, inhibiting TGF-beta signals greatly enhanced surface expression of GARP on Tregs and blocked the induction of Foxp3 in activated CD4(+) T cells overexpressing GARP. These findings suggest a role for GARP in natural and induced Treg development through activation of bound latent TGF-beta and signaling, which negatively regulates GARP expression on Tregs. |
