Cutting Edge: Immature human dendritic cells express latency-associated peptide and inhibit T cell activation in a TGF-beta-dependent manner.
Dendritic cells (DCs) play a critical role in both initiating immune responses and in maintaining peripheral tolerance. However, the exact mechanism by which DCs instruct/influence the generation of effector vs regulatory T cells is not clear. In this study, we present evidence that TGF-beta, an important immunoregulatory molecule, is present on the surface of ex vivo immature human DCs bound by latency-associated peptide (LAP). Maturation of DCs upon stimulation with LPS results in loss of membrane-bound LAP and up-regulation of HLA class II and costimulatory molecules. The presence of LAP on immature DCs selectively inhibits Th1 cell but not Th17 cell differentiation and is required for differentiation and/or survival of Foxp3-positive regulatory T cells. Taken together, our results indicate that surface expression of TGF-beta on DCs in association with LAP is one of the mechanisms by which immature DCs limit T cell activation and thus prevent autoimmune responses.
Gandhi
Roopali
R
Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Anderson
David E
DE
Weiner
Howard L
HL
D000906:Antibodies / Q000494:pharmacology; D015551:Autoimmunity; D002454:Cell Differentiation; D016764:Cell Polarity; D049109:Cell Proliferation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D034741:RNA, Small Interfering / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000906:Antibodies; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma