Lymphocyte-mediated Immune Regulation in Health and Disease: The Treg and γδ T Cell Co-conspiracy.

The significance of lymphocytes functioning to mediate immunological tolerance has garnered increasing appreciation during the last several decades. CD4+ CD25+ α/ β T cells have arguably been the most extensively studied regulatory lymphocyte to date, perhaps owing to the dramatic phenotype observed mice and humans with mutated Foxp3. However, emerging studies suggest that the lineage of regulatory lymphocytes is quite robust. Most notably, while γδ T cells are more traditionally regarded as mediators of cytotoxic function, they are beginning to be regarded as potential negative regulators of immunity. While regulatory γ/δ T cells may possess a degree of transcriptional overlap with 'classical Tregs', there remains less clarity in regard to the mechanisms driving the suppressive potential of these cells. In this review, I will discuss the role of Tregs in establishing tolerance in the steady state as well as disease, and how their accumulation and function may be modulated by myeloid cells in the local microenvironment. I will also discuss the necessity to extend our understanding of the regulatory nature of γδ T cells, which may lead to the unearthing of novel paradigms of immunity, perhaps most notably with respect to cancer.