Nature Medicine
- 12, 518 - 525 (2006)
Published online: 23 April 2006; | doi:10.1038/nm1402
Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAEYawei Liu1, Ingrid Teige1, Bryndis Birnir2 & Shohreh Issazadeh-Navikas11
Neuroinflammation Unit, Institute for Experimental Medical Science, University of Lund, BMC, I13, 221 84 Lund, Sweden. 2
Department of Clinical Sciences, Clinical Research Center, University of Lund, 91-11-59, 205 02, Malmö, Sweden.
Correspondence should be addressed to Shohreh Issazadeh-Navikas shohreh.issazadeh@med.lu.se 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)- 1–TGF- 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-1+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-1. Autocrine action of TGF-1, however, is important for the proliferative arrest of Treg cells. Blocking the B7 and TGF- 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.
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