The Family of IL-10-Secreting CD4+ T Cells

Regulatory T cells (Treg cells) play critical roles in the induction of peripheral tolerance to self- and foreign antigens. Naturally occurring CD4+CD25+ Treg cells, which characteristically express the transcription factor forkhead box protein P3 (Foxp3), have been studied intensively because their deficiency abrogates self-tolerance and causes autoimmune disease. However, several lines of evidence suggest that additional important mechanisms other than the Foxp3 system are required to enforce immunological self-tolerance in the periphery. Interleukin-10 (IL-10) is a regulatory cytokine that plays a central role in controlling inflammatory processes, and IL-10-secreting T cells may constitute an additional mechanism that are responsible for peripheral tolerance. Type-1 T regulatory (Tr1) cells, CD46-stimulated IL-10-secreting T cells, and IL-10-secreting T cells induced by vitamin D3 (VitD3) and dexamethasone (Dex) are induced populations with significant regulatory activities. However, assessing the detailed physiological function of these cells is difficult, because of the lack of specific markers that can reliably differentiate the population of IL-10-secreting Treg cells from other T cells. Recently, CD4+CD25−LAP+ T cells, CD4+NKG2D+ T cells, CD4+IL-7R− T cells, and CD4+CD25−LAG3+ T cells have been reported as naturally present IL-10-secreting Treg cells. Although the relationship between these induced and naturally present IL-10-secreting Treg cells is unclear, elucidation of their respective roles in modulating immune responses is crucial to understand T cell-mediated tolerance. Furthermore, the identification of specific markers and molecular signatures will enable the purification or induction of IL-10-secreting Treg cells for the treatment of patients having inflammatory diseases.