ICOS and CD28 reversely regulate IL-10 on re-activation of human effector T cells with mature dendritic cells.
With newly generated ICOS-ligand (ICOS-L)-specific monoclonal antibodies we determined that human Langerhans cells in situ express similar levels of ICOS-L, CD80, and CD86, compared to immature dendritic cells (DC) derived from monocytes in vitro. Maturation of DC strongly up-regulated CD80 and CD86 but did not significantly change ICOS-L levels. On coculture of "naive"CD4(+) T cells with mature DC in the presence of superantigen, ICOS was highly up-regulated on T cells, but played only a secondary role in the CD28-dominated release of TNF-alpha and IFN-gamma, and did not participate in the induction of IL-2. Cocultures of "effector" CD4(+) T cells with mature DC revealed CD28 as the driving force for the secretion of IL-2, IFN-gamma, IL-6, and IL-13, with no apparent contribution of ICOS. In contrast, the release of IL-10 was differentially regulated. Interaction of ICOS with ICOS-L strongly promoted IL-10 secretion, whereas the CD28/B7 pathway acted as a potent attenuator of IL-10 release. Our data thus indicate a selective regulation of IL-10 secretion by ICOS on re-activation of effector T cells with professional antigen-presenting cells (bearing CD80 and CD86) in lymphoid tissue.
Molecular Immunology, Robert Koch-Institute, Berlin, Germany.
Esther J
EJ
Witsch
Matthias
M
Peiser
Andreas
A
Hutloff
Kerstin
K
Büchner
Brigitte G
BG
Dorner
Helmut
H
Jonuleit
Hans W
HW
Mages
Richard A
RA
Kroczek
D000069594:Abatacept; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D000943:Antigens, Differentiation / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D060908:CTLA-4 Antigen; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D000078404:Epidermal Cells; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D018796:Immunoconjugates; D007074:Immunoglobulin G / Q000276:immunology; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D007801:Langerhans Cells / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D014176:Protein Biosynthesis; D011506:Proteins / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; C556692:ICOS protein, human; C498514:ICOSLG protein, human; C556694:Icos protein, mouse; C400230:Icosl protein, mouse; D018796:Immunoconjugates; D007074:Immunoglobulin G; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D007378:Interleukins; D008562:Membrane Glycoproteins; D011506:Proteins; D016753:Interleukin-10; D000069594:Abatacept; D007371:Interferon-gamma