Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo

• DOI: 10.1084/jem.20120822
• Publication Date: 2012-09-11T05:39:31Z
• Authors: Mahesh Yadav; Cedric Louvet; Dan Davini; James M. Gardner; Marc Martinez-Llo...; Samantha Bailey-B...; Bryan A. Anthony; Francis M. Sverdrup; Richard Head; Daniel J. Kuster; Peter Ruminski; David Weiss; David Von Schack; Jeffrey A. Bluestone
• Keywords: Male; Biomedical and clinical sciences; Lymphoid Tissue; 1.1 Normal biological development and functioning; T-Lymphocytes; Immunology; Receptors, Antigen, T-Cell; 610; Autoimmunity; Mice, Transgenic; Inbred C57BL; Lymphocyte Activation; Autoimmune Disease; Medical and Health Sciences; T-Lymphocytes, Regulatory; Transgenic; Mice; Underpinning research; Mice, Inbred NOD; T-Lymphocyte Subsets; Receptors; Animals; Biomedical and Clinical Sciences; Inflammatory and immune system; Brief Definitive Report; 500; Health sciences; Myelin Basic Protein; T-Cell; Regulatory; Neuropilin-1; Mice, Inbred C57BL; Gene Expression Regulation; Antigen; Inbred NOD

Foxp3+ CD4+ T helper cells called regulatory T (T reg) cells play a key role in controlling reactivity to self-antigens and onset of autoimmunity. T reg cells either arise in thymus and are called natural T reg (nT reg) cells or are generated in the periphery through induction of Foxp3 and are called inducible T reg (iT reg) cells. The relative contributions of iT reg cells and nT reg cells in peripheral tolerance remain unclear as a result of an inability to separate these two subsets of T reg cells. Using a combination of novel TCR transgenic mice with a defined self-antigen specificity and conventional mouse models, we demonstrate that a cell surface molecule, neuropilin-1 (Nrp-1), is expressed at high levels on nT reg cells and can be used to separate nT reg versus iT reg cells in certain physiological settings. In addition, iT reg cells generated through antigen delivery or converted under homeostatic conditions lack Nrp-1 expression. Nrp-1lo iT reg cells show similar suppressive activity to nT reg cells in controlling ongoing autoimmune responses under homeostatic conditions. In contrast, their activity might be compromised in certain lymphopenic settings. Collectively, our data show that Nrp-1 provides an excellent marker to distinguish distinct T reg subsets and will be useful in studying the role of nT reg versus iT reg cells in different disease settings.