Novel CD8(+) regulatory T cells suppress experimental autoimmune encephalomyelitis by TGF-beta- and IFN-gamma-dependent mechanisms. Export

@article{citeulike:5843795, abstract = {Although CD8(+) regulatory T cell (Treg)-mediated suppression has been described, CD8(+) Treg remain poorly characterized. Here we identify a novel subset of CD8(+) Treg that express latency-associated peptide (LAP) on their cell surface (CD8(+)LAP(+) cells) and exhibit regulatory activity in vitro and in vivo. Only a small fraction of CD8(+)LAP(+) cells express forkhead box P3 (Foxp3) or CD25, although the expression levels of Foxp3 for these cells are higher than their LAP(-) counterparts. In addition to TGF-beta, CD8(+)LAP(+) cells produce IFN-gamma, and these cells suppress experimental autoimmune encephalomyelitis (EAE) that is dependent on both TGF-beta and IFN-gamma. In an adoptive co-transfer model, CD8(+)LAP(+) cells suppress myelin oligodendrocyte glycoprotein (MOG)-specific immune responses by inducing or expanding Foxp3(+) cells and by inhibiting proliferation and IFN-gamma production in vivo. Furthermore, in vivo neutralization of IFN-gamma and studies with IFN-gamma-deficient mice demonstrate an important role for IFN-gamma production in the function of CD8(+)LAP(+) cells. Our findings identify the underlying mechanisms that account for the immunoregulatory activity of CD8(+) T cells and suggest that induction or amplification of CD8(+)LAP(+) cells may be a therapeutic strategy to help control autoimmune processes.}, author = {Chen, Mei-Ling L. and Yan, Bo-Shiun S. and Kozoriz, Deneen and Weiner, Howard L.}, citeulike-article-id = {5843795}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/eji.200939441}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19768696}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19768696}, day = {18}, doi = {10.1002/eji.200939441}, issn = {1521-4141}, journal = {European journal of immunology}, keywords = {cd8\_t\_cells, eae, ifn-gamma, regulatory\_mechanisms, tgf-beta, treg\_cells}, month = {September}, posted-at = {2009-09-26 18:24:07}, priority = {2}, title = {Novel CD8(+) regulatory T cells suppress experimental autoimmune encephalomyelitis by TGF-beta- and IFN-gamma-dependent mechanisms.}, url = {http://dx.doi.org/10.1002/eji.200939441}, year = {2009} }

TY - JOUR ID - citeulike:5843795 L3 - citeulike-article-id:5843795 N2 - Although CD8(+) regulatory T cell (Treg)-mediated suppression has been described, CD8(+) Treg remain poorly characterized. Here we identify a novel subset of CD8(+) Treg that express latency-associated peptide (LAP) on their cell surface (CD8(+)LAP(+) cells) and exhibit regulatory activity in vitro and in vivo. Only a small fraction of CD8(+)LAP(+) cells express forkhead box P3 (Foxp3) or CD25, although the expression levels of Foxp3 for these cells are higher than their LAP(-) counterparts. In addition to TGF-beta, CD8(+)LAP(+) cells produce IFN-gamma, and these cells suppress experimental autoimmune encephalomyelitis (EAE) that is dependent on both TGF-beta and IFN-gamma. In an adoptive co-transfer model, CD8(+)LAP(+) cells suppress myelin oligodendrocyte glycoprotein (MOG)-specific immune responses by inducing or expanding Foxp3(+) cells and by inhibiting proliferation and IFN-gamma production in vivo. Furthermore, in vivo neutralization of IFN-gamma and studies with IFN-gamma-deficient mice demonstrate an important role for IFN-gamma production in the function of CD8(+)LAP(+) cells. Our findings identify the underlying mechanisms that account for the immunoregulatory activity of CD8(+) T cells and suggest that induction or amplification of CD8(+)LAP(+) cells may be a therapeutic strategy to help control autoimmune processes. JF - European journal of immunology SN - 1521-4141 TI - Novel CD8(+) regulatory T cells suppress experimental autoimmune encephalomyelitis by TGF-beta- and IFN-gamma-dependent mechanisms. KW - cd8_t_cells KW - eae KW - ifn-gamma KW - regulatory_mechanisms KW - tgf-beta KW - treg_cells AU - Chen, Mei-Ling AU - Yan, Bo-Shiun AU - Kozoriz, Deneen AU - Weiner, Howard PY - 2009/09/18/ UR - http://dx.doi.org/10.1002/eji.200939441 ER -