Antigen-presenting cell-derived signals determine expression levels of CD70 on primed T cells.
Interaction between CD27 and its ligand CD70 provides a second signal for T-cell proliferation and tumour necrosis factor-alpha (TNF-alpha) production. Whereas CD27 is broadly expressed during T-cell development, expression of CD70 in vivo is restricted. To determine when CD27 CD70 interactions can occur in immune reactions, we here analysed the regulation of CD70 expression on activated T cells. Mitogenic stimulation of purified T cells with either immobilized CD3 monoclonal antibody (mAb) or a combination of CD2 mAb induces only low levels of CD70 membrane expression. Markedly expression of the CD27-ligand is strongly enhanced by antigen-presenting cells (APC) and APC-associated signals such as interleukin-1 alpha (IL-1 alpha). IL-12, TNF-alpha and CD28-ligation. In contrast, T-cell derived cytokines, such as IL-4, counteract CD70 up-regulation on activated T cells. Analysis of the small subset of circulating CD70+ T cells revealed that these cells have a primed phenotype as they express CD45RO and HLA-DR antigens and are in high frequency able to secrete interferon-gamma (IFN-gamma). We conclude that T-T interactions involving CD27 and CD70 are likely to occur relatively early in immune reactions, after productive T-cell priming by APC and that expression of CD70 on circulating T cells is a reflection of recent priming by antigen.
Lens
S M
SM
Department of Clinical (Viro)-Immunology, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam, The Netherlands.
Baars
P A
PA
Hooibrink
B
B
van Oers
M H
MH
van Lier
R A
RA
D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD; D018801:CD2 Antigens / Q000276:immunology; D053282:CD27 Ligand; D018929:Cell Culture Techniques; D016207:Cytokines / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018801:CD2 Antigens; D053282:CD27 Ligand; C505771:CD70 protein, human; D016207:Cytokines; D008565:Membrane Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D007371:Interferon-gamma