Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAE.
Research output: Contribution to journal › Journal article › Research › peer-review
Neurons have been neglected as cells with a major immune-regulatory function because they do not express major histocompatibility complex class II. Our data show that neurons are highly immune regulatory, having a crucial role in governing T-cell response and central nervous system (CNS) inflammation. Neurons induce the proliferation of activated CD4+ T cells through B7-CD28 and transforming growth factor (TGF)-beta1-TGF-beta receptor signaling pathways, resulting in amplification of T-cell receptor signaling through phosphorylated ZAP-70, interleukin (IL)-2 and IL-9. The interaction between neurons and T cells results in the conversion of encephalitogenic T cells to CD25+ TGF-beta1+ CTLA-4+ FoxP3+ T regulatory (Treg) cells that suppress encephalitogenic T cells and inhibit experimental autoimmune encephalomyelitis. Suppression is dependent on cytotoxic T lymphocyte antigen (CTLA)-4 but not TGF-beta1. Autocrine action of TGF-beta1, however, is important for the proliferative arrest of Treg cells. Blocking the B7 and TGF-beta pathways prevents the CNS-specific generation of Treg cells. These findings show that generation of neuron-dependent Treg cells in the CNS is instrumental in regulating CNS inflammation.
Original language | English |
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Journal | Nature Medicine |
Volume | 12 |
Issue number | 5 |
Pages (from-to) | 518-25 |
Number of pages | 7 |
ISSN | 1078-8956 |
DOIs | |
Publication status | Published - 2006 |
Bibliographical note
Keywords: Animals; Antigens, CD; Antigens, CD80; Antigens, Differentiation; Cell Line; Cell Proliferation; Coculture Techniques; Encephalomyelitis, Autoimmune, Experimental; Mice; Mice, Inbred Strains; Mice, Transgenic; Neurons; Receptors, Antigen, T-Cell; Signal Transduction; T-Lymphocytes, Regulatory; Transforming Growth Factor beta; Transforming Growth Factor beta1
ID: 5122566