Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5667934 | Journal of Autoimmunity | 2017 | 10 Pages |
â¢CD4+CD25âLAG3+ T cells compose a distinct T cell subset in the human tonsil.â¢Tonsillar CD4+CD25âLAG3+ T cells suppress antibody production more efficiently than CD4+CD25+ T cells.â¢Cell contact is important for suppression by tonsillar CD4+CD25âLAG3+ T cells.â¢Tonsillar CD4+CD25âLAG3+ T cells suppress graft-versus-host disease (GVHD) reactions in humanized mice.â¢Tonsillar CD4+CD25âLAG3+ T cells are a subset of naturally occurring IL-10-producing Tregs.
IL-10-producing regulatory T cells (IL-10-producing Tregs) are one of the regulatory T cell subsets characterized by the production of high amounts of IL-10, the lack of FOXP3 expression and the strong immunosuppressive capabilities. IL-10-producing Tregs have been primarily reported as induced populations thus far, in part because identifying naturally occurring IL-10-producing Tregs was difficult due to the lack of definitive surface markers. Lymphocyte-activation gene 3 (LAG3) is a CD4 homologue that we have identified as being expressed on IL-10 producing Tregs. In human PBMC, LAG3 combined with CD49b efficiently identifies IL-10-producing Tregs. However, naturally occurring IL-10-producing Tregs in human secondary lymphoid tissue have not been described.In this report, we identified CD4+CD25âLAG3+ T cells in human tonsil. This T cell subset produced high amounts of IL-10 and expressed low levels of FOXP3. Surface markers and microarray analysis revealed that this is a distinct tonsillar CD4+ T cell subset. CD4+CD25âLAG3+ T cells expressed interleukin 10 (IL10), PR/SET domain 1 (PRDM1), and CD274 at high levels and chemokine receptor 5 (CXCR5) at low levels. CD4+CD25âLAG3+ T cells suppressed antibody production more efficiently than CD4+CD25+ T cells, and CD4+CD25âLAG3+ T cells induced B cell apoptosis. Moreover, analysis of humanized mice revealed that this cell subset suppressed a graft-versus-host disease (GVHD) reaction in vivo. Our study reveals the existence of naturally occurring IL-10-producing Tregs in human secondary lymphoid tissue and their function in immune regulation.