TY - JOUR
T1 - CD8α+ dendritic cells prime TCR-peptide-reactive regulatory CD4+FOXP3- T cells
AU - Ria, Francesco
PY - 2010
Y1 - 2010
N2 - CD4+ T cells with immune regulatory function can be either FOXP3+ or FOXP3-. We have previously shown that priming of naturally occurring TCR-peptide-reactive CD4+FOXP3- Treg specifically controls Vβ8.2+CD4+ T cells mediating EAE. However, the mechanism by which these Treg are primed to recognize their cognate antigenic determinant, which is derived from the TCRVβ8.2-chain, is not known. In this study we show that APC derived from splenocytes of naïve mice are able to stimulate cloned CD4+ Treg in the absence of exogenous antigen, and their stimulation capacity is augmented during EAE. Among the APC populations, DC were the most efficient in stimulating the Treg. Stimulation of CD4+ Treg was dependent upon processing and presentation of TCR peptides from ingested Vβ8.2TCR+CD4 + T cells. Additionally, DC pulsed with TCR peptide or apoptotic Vβ8.2+ T cells were able to prime Treg in vivo and mediate protection from disease in a CD8-dependent fashion. These data highlight a novel mechanism for the priming of CD4+ Treg by CD8α+ DC and suggest a pathway that can be exploited to prime antigen-specific regulation of T-cell-mediated inflammatory disease. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.
AB - CD4+ T cells with immune regulatory function can be either FOXP3+ or FOXP3-. We have previously shown that priming of naturally occurring TCR-peptide-reactive CD4+FOXP3- Treg specifically controls Vβ8.2+CD4+ T cells mediating EAE. However, the mechanism by which these Treg are primed to recognize their cognate antigenic determinant, which is derived from the TCRVβ8.2-chain, is not known. In this study we show that APC derived from splenocytes of naïve mice are able to stimulate cloned CD4+ Treg in the absence of exogenous antigen, and their stimulation capacity is augmented during EAE. Among the APC populations, DC were the most efficient in stimulating the Treg. Stimulation of CD4+ Treg was dependent upon processing and presentation of TCR peptides from ingested Vβ8.2TCR+CD4 + T cells. Additionally, DC pulsed with TCR peptide or apoptotic Vβ8.2+ T cells were able to prime Treg in vivo and mediate protection from disease in a CD8-dependent fashion. These data highlight a novel mechanism for the priming of CD4+ Treg by CD8α+ DC and suggest a pathway that can be exploited to prime antigen-specific regulation of T-cell-mediated inflammatory disease. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.
KW - Animals
KW - Antigen Presentation
KW - Antigen presentation/processing
KW - Apoptosis
KW - CD4 Antigens
KW - CD8 Antigens
KW - Clone Cells
KW - DC
KW - Dendritic Cells
KW - EAE/MS
KW - Encephalomyelitis, Autoimmune, Experimental
KW - Female
KW - Forkhead Transcription Factors
KW - Humans
KW - Immunization
KW - Immunology
KW - Immunology and Allergy
KW - Lymphocyte Activation
KW - Mice
KW - Mice, Inbred Strains
KW - Myelin Basic Protein
KW - Peptide Fragments
KW - Receptors, Antigen, T-Cell, alpha-beta
KW - T-Cell Antigen Receptor Specificity
KW - T-Lymphocytes, Regulatory
KW - TCR
KW - Tolerance/suppression/anergy
KW - Animals
KW - Antigen Presentation
KW - Antigen presentation/processing
KW - Apoptosis
KW - CD4 Antigens
KW - CD8 Antigens
KW - Clone Cells
KW - DC
KW - Dendritic Cells
KW - EAE/MS
KW - Encephalomyelitis, Autoimmune, Experimental
KW - Female
KW - Forkhead Transcription Factors
KW - Humans
KW - Immunization
KW - Immunology
KW - Immunology and Allergy
KW - Lymphocyte Activation
KW - Mice
KW - Mice, Inbred Strains
KW - Myelin Basic Protein
KW - Peptide Fragments
KW - Receptors, Antigen, T-Cell, alpha-beta
KW - T-Cell Antigen Receptor Specificity
KW - T-Lymphocytes, Regulatory
KW - TCR
KW - Tolerance/suppression/anergy
UR - http://hdl.handle.net/10807/117668
UR - http://www3.interscience.wiley.com/cgi-bin/fulltext/123350929/pdfstart
U2 - 10.1002/eji.200939608
DO - 10.1002/eji.200939608
M3 - Article
SN - 0014-2980
VL - 40
SP - 1906
EP - 1915
JO - European Journal of Immunology
JF - European Journal of Immunology
ER -