CD27-CD70 interactions sensitise naive CD4+ T cells for IL-12-induced Th1 cell development.
Stimulation of CD27, a member of the tumour necrosis factor receptor family, by its ligand CD70 induces expansion of IFNgamma secreting CD4+ and CD8+ T cells in vivo. We here analysed the mechanisms through which CD27 mediates this effect. CD27 co-stimulation induced cell division but did not directly instruct naive CD4+ T cells to differentiate into IFNgamma-producing Th1 cells. Rather, in concert with signals delivered through the TCR-CD3 complex, CD27 co-stimulation enhanced the Th1-specific transcription factor T-bet and caused up-regulation of the IL-12Rbeta2 chain. Consequently, CD27-costimulated T cells yielded vast numbers of IFNgamma-secreting cells in response to IL-12. Additionally, CD27 ligation induced a strong up-regulation of Bcl-xL, but not of related anti-apoptotic molecules. Thus, CD27-CD70 interactions may promote Th1 formation by permitting naive T cells to respond to differentiation signals and by promoting survival of activated effector T cells.
van Oosterwijk
Michiel F
MF
Department of Experimental Immunology, Academic Medical Centre, Amsterdam, The Netherlands.
Juwana
Hedi
H
Arens
Ramon
R
Tesselaar
Kiki
K
van Oers
Marinus H J
MH
Eldering
Eric
E
van Lier
René A W
RA
D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D053282:CD27 Ligand / Q000235:genetics / Q000378:metabolism*; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology*; D053712:Interleukin-12 Receptor beta 2 Subunit / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D011485:Protein Binding; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000378:metabolism*; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism; D000098815:T-bet Transcription Factor
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C494811:BCL2L1 protein, human; D053282:CD27 Ligand; D017252:CD3 Complex; D053712:Interleukin-12 Receptor beta 2 Subunit; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D051020:bcl-X Protein; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma