Induction of FOXP3-expressing regulatory CD4(pos) T cells by human mature autologous dendritic cells

V. Verhasselt, O Vosters, C Beuneu, C Nicaise, P Stordeur, M Goldman

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

Current literature suggests that T cells recognizing antigen on mature dendritic cells (DC) differentiate into effector T cells whereas tolerance is induced when antigen is presented by immature DC. We investigated the consequences of the interactions between immature or lipopolysaccharide-matured DC and CD4(pos) T lymphocytes in absence of foreign antigen. While immature DC did not induce significant CD4(pos) T cell activation, we observed that a significant fraction of CD4(pos) T cells cultured with mature autologous DC displayed phenotypic features of activation and produced IL-2, IFN-gamma, IL-10 and TGF-beta. Furthermore, CD4(pos) T lymphocytes primed by mature, but not immature, autologous DC acquired regulatory properties. Indeed, when added to an allogeneic mixed leukocyte reaction, they suppressed the response of alloreactive T lymphocytes to the priming DC while responses to third-party stimulators were spared. The generation of CD4(pos) T cells with regulatory function by autologous stimulation did not require the presence of natural CD4(pos)CD25(pos) regulatory T cells. In addition, the acquisition of regulatory function by CD4(pos)CD25(neg) T cells stimulated by autologous mature DC was accompanied by the induction of FOXP3 expression. Our data suggest that during inflammatory conditions, presentation of self antigens by mature DC to autologous T lymphocytes could contribute to the generation of regulatory mechanisms.

Original languageEnglish
Pages (from-to)762-772
Number of pages11
JournalEuropean Journal of Immunology
Volume34
Issue number3
DOIs
Publication statusPublished - Mar 2004

Cite this

Verhasselt, V. ; Vosters, O ; Beuneu, C ; Nicaise, C ; Stordeur, P ; Goldman, M. / Induction of FOXP3-expressing regulatory CD4(pos) T cells by human mature autologous dendritic cells. In: European Journal of Immunology. 2004 ; Vol. 34, No. 3. pp. 762-772.
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abstract = "Current literature suggests that T cells recognizing antigen on mature dendritic cells (DC) differentiate into effector T cells whereas tolerance is induced when antigen is presented by immature DC. We investigated the consequences of the interactions between immature or lipopolysaccharide-matured DC and CD4(pos) T lymphocytes in absence of foreign antigen. While immature DC did not induce significant CD4(pos) T cell activation, we observed that a significant fraction of CD4(pos) T cells cultured with mature autologous DC displayed phenotypic features of activation and produced IL-2, IFN-gamma, IL-10 and TGF-beta. Furthermore, CD4(pos) T lymphocytes primed by mature, but not immature, autologous DC acquired regulatory properties. Indeed, when added to an allogeneic mixed leukocyte reaction, they suppressed the response of alloreactive T lymphocytes to the priming DC while responses to third-party stimulators were spared. The generation of CD4(pos) T cells with regulatory function by autologous stimulation did not require the presence of natural CD4(pos)CD25(pos) regulatory T cells. In addition, the acquisition of regulatory function by CD4(pos)CD25(neg) T cells stimulated by autologous mature DC was accompanied by the induction of FOXP3 expression. Our data suggest that during inflammatory conditions, presentation of self antigens by mature DC to autologous T lymphocytes could contribute to the generation of regulatory mechanisms.",
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Induction of FOXP3-expressing regulatory CD4(pos) T cells by human mature autologous dendritic cells. / Verhasselt, V.; Vosters, O; Beuneu, C; Nicaise, C; Stordeur, P; Goldman, M.

In: European Journal of Immunology, Vol. 34, No. 3, 03.2004, p. 762-772.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Induction of FOXP3-expressing regulatory CD4(pos) T cells by human mature autologous dendritic cells

AU - Verhasselt, V.

AU - Vosters, O

AU - Beuneu, C

AU - Nicaise, C

AU - Stordeur, P

AU - Goldman, M

PY - 2004/3

Y1 - 2004/3

N2 - Current literature suggests that T cells recognizing antigen on mature dendritic cells (DC) differentiate into effector T cells whereas tolerance is induced when antigen is presented by immature DC. We investigated the consequences of the interactions between immature or lipopolysaccharide-matured DC and CD4(pos) T lymphocytes in absence of foreign antigen. While immature DC did not induce significant CD4(pos) T cell activation, we observed that a significant fraction of CD4(pos) T cells cultured with mature autologous DC displayed phenotypic features of activation and produced IL-2, IFN-gamma, IL-10 and TGF-beta. Furthermore, CD4(pos) T lymphocytes primed by mature, but not immature, autologous DC acquired regulatory properties. Indeed, when added to an allogeneic mixed leukocyte reaction, they suppressed the response of alloreactive T lymphocytes to the priming DC while responses to third-party stimulators were spared. The generation of CD4(pos) T cells with regulatory function by autologous stimulation did not require the presence of natural CD4(pos)CD25(pos) regulatory T cells. In addition, the acquisition of regulatory function by CD4(pos)CD25(neg) T cells stimulated by autologous mature DC was accompanied by the induction of FOXP3 expression. Our data suggest that during inflammatory conditions, presentation of self antigens by mature DC to autologous T lymphocytes could contribute to the generation of regulatory mechanisms.

AB - Current literature suggests that T cells recognizing antigen on mature dendritic cells (DC) differentiate into effector T cells whereas tolerance is induced when antigen is presented by immature DC. We investigated the consequences of the interactions between immature or lipopolysaccharide-matured DC and CD4(pos) T lymphocytes in absence of foreign antigen. While immature DC did not induce significant CD4(pos) T cell activation, we observed that a significant fraction of CD4(pos) T cells cultured with mature autologous DC displayed phenotypic features of activation and produced IL-2, IFN-gamma, IL-10 and TGF-beta. Furthermore, CD4(pos) T lymphocytes primed by mature, but not immature, autologous DC acquired regulatory properties. Indeed, when added to an allogeneic mixed leukocyte reaction, they suppressed the response of alloreactive T lymphocytes to the priming DC while responses to third-party stimulators were spared. The generation of CD4(pos) T cells with regulatory function by autologous stimulation did not require the presence of natural CD4(pos)CD25(pos) regulatory T cells. In addition, the acquisition of regulatory function by CD4(pos)CD25(neg) T cells stimulated by autologous mature DC was accompanied by the induction of FOXP3 expression. Our data suggest that during inflammatory conditions, presentation of self antigens by mature DC to autologous T lymphocytes could contribute to the generation of regulatory mechanisms.

KW - dendritic cells

KW - CD4(pos)

KW - T lymphocytes

KW - lipopolysaccharide

KW - suppression

KW - autologous MLR

KW - MIXED LYMPHOCYTE-REACTION

KW - IN-VIVO

KW - COSTIMULATORY MOLECULES

KW - AUTOIMMUNE-DISEASE

KW - ADJUVANT ARTHRITIS

KW - SELF-RECOGNITION

KW - STEADY-STATE

KW - NOD MICE

KW - EXPRESSION

KW - GENERATION

U2 - 10.1002/eji.200324552

DO - 10.1002/eji.200324552

M3 - Article

VL - 34

SP - 762

EP - 772

JO - European Journal Immunology

JF - European Journal Immunology

SN - 0014-2980

IS - 3

ER -