The Cellular and Molecular Mechanisms of Immuno-Suppression by Human Type 1 Regulatory T Cells

Abstract

The immuno-regulatory mechanisms of IL-10-producing type 1 regulatory T (Tr1) cells have been widely studied over the years. However, several recent discoveries have shed new light on the cellular and molecular mechanisms that human Tr1 cells use to control immune responses and induce tolerance. In this review we outline the well known and newly discovered regulatory properties of human Tr1 cells and provide an in-depth comparison of the known suppressor mechanisms of Tr1 cells with FOXP3+ Treg. We also highlight the role that Tr1 cells play in promoting and maintaining tolerance in autoimmunity, allergy, and transplantation.

Type 1 regulatory T cells: a new mechanism of peripheral immune tolerance

“…The expression levels of different co-stimulatory or inhibitory molecules such as CTLA-4, PD-1, and ICOS in Tr1 cells exerted immunomodulatory effects similar to traditional Foxp3 1 T reg in this pathway. 56,57 The PD-1/PD-L pathway mediated by cell-cell contact between Tr1 cells and APCs indirectly inhibits the activation and proliferation of self-reactive T cells. 58,59 In this process, the CTLA-4/CD80 pathway exhibited a synergistic effect.…”

Immunomodulatory effects of inosine pranobex on cytokine production by human lymphocytes

“…IL-10 is a broadly expressed cytokine playing a dominant role in suppression of innate and adaptive immunity (20) and is produced mainly by monocytes and macrophages but also by lymphoid cells such as Th2, Tgd cells, and B lymphocytes (14,(20)(21)(22)(23), and, under certain conditions, by Th1 cells (22,23). It belongs classically to the group of Th2-type cytokines but in humans it is also produced in large amounts by a subset of regulatory T cells -Tr1 lymphocytes (20,24). Although it cannot be excluded that small quantities of IL-10 in supernatants in our experiments derive from residual phagocytic cells (monocytes), the strong dependence of IL-10 production on the presence of PHA in cultures clearly shows that the primary source of this cytokine are lymphocytes.…”

CD4+CD25hiCD127− Treg and CD4+CD45R0+CD49b+LAG3+ Tr1 cells in bone marrow and peripheral blood samples from children with neuroblastoma

“…12 Subsequently, Tr1 cells have been characterized in humans, [13][14][15] and are now identified as CD4 C CD45R0 C CD49b C LAG-3 C T cells. 16 Only recently the presence of Tr1 cells was documented in tumor patients.…”