Although, previous works suggested that the Treg cells that develop in absence of CTLA-4 have acquired compensatory suppressive mechanisms through enhanced TGF-β- or IL-10-dependent pathways (49, 50), one study revealed a non-redundant role for CTLA-4 expression by Treg cells to limit lymphopenia-induced CD4 T-cell expansion in vivo, which seems to be independent of IL-10, IL-35, TGF-β, or IDO (51). This evidence concerns the gene TGFB1 and lymphopenia.