Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAE.

TY - JOUR

T1 - Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAE.

AU - Liu, Yawei

AU - Teige, Ingrid

AU - Birnir, Bryndis

AU - Issazadeh-Navikas, Shohreh

N1 - 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

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

U2 - 10.1038/nm1402

DO - 10.1038/nm1402

M3 - Journal article

C2 - 16633347

SN - 1078-8956

VL - 12

SP - 518

EP - 525

JO - Nature Medicine

JF - Nature Medicine

IS - 5

ER -