T cell-intrinsic TLR2 stimulation promotes IL-10 expression and suppressive activity by CD45RbHi T cells

• Published in: PloS one Vol. 12; no. 7; p. e0180688
• Main Authors: Jun, Janice C, Jones, Mark B, Oswald, Douglas M, Sim, Edward S, Jonnalagadda, Amruth R, Kreisman, Lori S C, Cobb, Brian A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 2017; Public Library of Science (PLoS)
• Subjects: Animals; Antigens; Biology and Life Sciences; CD25 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD44 antigen; Cell differentiation; Cells, Cultured; Cytokines; Differentiation (biology); Effector cells; Epithelial cells; Female; Foxp3 protein; Immune system; Immunological memory; Immunoregulation; Interleukin 10; Interleukin-10 - immunology; Interleukin-2 Receptor alpha Subunit - immunology; L-selectin; Leukocyte Common Antigens - immunology; Leukocytes; Lymphocytes; Lymphocytes T; Male; Medical prognosis; Medicine; Medicine and Health Sciences; Memory cells; Mice, Inbred C57BL; Pathology; Proteins; Receptors; Receptors, Antigen, T-Cell - immunology; Research and Analysis Methods; Stimulation; T cell receptors; T-cell receptor; T-Lymphocytes, Regulatory - immunology; TLR2 protein; Toll-Like Receptor 2 - immunology; Toll-like receptors; Cleveland Ohio; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0180688

While Toll-like receptors (TLRs) represent one of the best characterized innate immune pathways, evidence suggests that TLRs are not restricted to innate leukocytes and some epithelial cells, but are also expressed in T cells. Specifically, published evidence focusing on FoxP3+ regulatory T cells demonstrate that they express functional TLR2, which is already known among the TLR family for its association with immune suppression; however, little is known about the relationship between T cell-intrinsic TLR2 binding and cytokine production, T cell differentiation, or T cell receptor (TCR) stimulation. Here, we demonstrate that TCR and TLR2 co-stimulation provides a T cell-intrinsic signal which generates a dramatic, synergistic cytokine response dominated by IL-10. Importantly, the response was not seen in either CD4+CD25+ or CD4+FoxP3+ Tregs, yet resulted in the expansion of a suppressive CD4+CD25+CD62L-CD44+CD45Rbhi effector/memory T cell subset not typically associated with immune inhibition. This study reveals the striking ability of a prototypical innate immune receptor to trigger a potent and suppressive IL-10 response in effector/memory T cells, supporting the notion that TLR2 is a co-regulatory receptor on T cells.