| First Author | Vogel I | Year | 2013 |
| Journal | Eur J Immunol | Volume | 43 |
| Issue | 4 | Pages | 1013-23 |
| PubMed ID | 23348953 | Mgi Jnum | J:195057 |
| Mgi Id | MGI:5476377 | Doi | 10.1002/eji.201242737 |
| Citation | Vogel I, et al. (2013) Foxp3(+) regulatory T cells are activated in spite of B7-CD28 and CD40-CD40L blockade. Eur J Immunol 43(4):1013-23 |
| abstractText | Costimulatory signals are required for priming and activation of naive T cells, while it is less clear how they contribute to induction of regulatory T (Treg)-cell activity. We previously reported that the blockade of the B7-CD28 and CD40L-CD40 interaction efficiently suppresses allogeneic T-cell activation in vivo. This was characterized by an initial rise in Foxp3(+) cells, followed by depletion of host-reactive T cells. To further investigate effects of costimulatory blockade on Treg cells, we used an in vitro model of allogeneic CD4(+) cell activation. When CTLA-4Ig and anti-CD40L mAb (MR1) were added to the cultures, T-cell proliferation and IL-2 production were strongly reduced. However, Foxp3(+) cells proliferated and acquired suppressive activity. They suppressed activation of syngeneic CD4(+) cells much more efficiently than did freshly isolated Treg cells. CD4(+) cells activated by allogeneic cells in the presence of MR1 and CTLA-4Ig were hyporesponsive on restimulation, but their response was restored to that of naive CD4(+) cells when Foxp3(+) Treg cells were removed. We conclude that natural Treg cells are less dependent on B7-CD28 or CD40-CD40L costimulation compared with Foxp3(-) T cells. Reduced costimulation therefore alters the balance between Teff and Treg-cell activation in favor of Treg-cell activity. |
