Follicular Lymphoma Intratumoral CD4+CD25+GITR+ Regulatory T Cells Potently Suppress CD3/CD28-Costimulated Autologous and Allogeneic CD8+CD25− and CD4+CD25− T Cells

摘要: Regulatory T cells (T R ) play a critical role in the inhibition of self-reactive immune responses and as such have been implicated suppression tumor-reactive effector cells. In this study, we demonstrate that follicular lymphoma (FL)-infiltrating CD8 + CD4 are hyporesponsive to CD3/CD28 costimulation. We further identify population FL-infiltrating CD25 GITR significantly overrepresented within FL nodes (FLN) compared with seen normal (nonmalignant, nonlymphoid hyperplastic) or reactive lymphoid nodes. These actively suppress both proliferation autologous nodal − cells, well cytokine production (IFN-γ, TNF-α IL-2), after Removal these vitro by magnetic bead depletion restores remaining demonstrating FLN cell hyporesponsiveness is reversible. addition suppressing also capable allogeneic from lymph donor PBL, regardless very robust stimulation target plate-bound anti-CD3 anti-CD28 Abs. The not reciprocal, equivalent numbers FOXP3 derived either PBL suggesting more suppressive than those nonmalignant sources. Lastly, TGF-β signaling partially mechanistic for -mediated suppression.