Clinical and diagnostic potential of regulatory T cell markers: From bench to bedside

Regulatory T (Treg) cells are heterogeneous immune cell populations residing in the thymus and peripheral lymphatic tissues. This immune cell plays a central and critical role in maintaining immune tolerance against undesirable immune responses. Treg cells' phenotypic heterogeneity caused by different pathological conditions makes their identification and differentiation from non-suppressive T cells difficult. On the other hand, using nonspecific markers and variable isolation panels leads to undesirable outcomes. There are a variety of markers to identify functional Treg cells, including CD25, FOXP3, and CTLA-4, as well as the epigenetic signature of forkhead box P3 (FOXP3), which can be used for both natural and induced Treg cells. Phenotypic heterogeneity is a major concern in Treg purification when using nonspecific markers, which can be addressed by utilizing suitable isolation panels designed for different purposes. This review presents a clinical framework for Treg detection and isolation, focusing on Treg markers such as CD25, FOXP3, CTLA-4, CD127, GPA-33, and TSDR demethylation to design Treg isolation panels suitable for different Treg therapy purposes. The current review also highlights new reliable Treg markers applicable for different purposes.