Differential expression and function of CD80 (B7-1) and CD86 (B7-2) on human peripheral blood monocytes.
The interaction of CD28 with its ligands is important for T-cell activation. Recent studies demonstrated the existence of at least two ligands on accessory cells, CD80 (B7-1) and CD86 (B7-2). In this study we demonstrate that, although CD80 and CD86 are both expressed on monocytes, they seem to have different functions. Freshly isolated monocytes express CD86 but are CD80-negative. CD80 expression is weakly induced after 6-8 hr of in vitro culture and is enhanced by stimulation. CD86 expression is enhanced faster than CD80 expression and reaches the peak level after 4-6 hr in stimulated cells. Reverse transcription-polymerase chain reaction studies demonstrate that freshly isolated monocytes contain no CD80-mRNA. The mRNA of CD80 is induced after 4-6 hr of culture, which matches with the expression of the protein. Inhibition studies using different antibodies against both molecules and the fusion protein CTLA4Ig show that only anti-CD80 and CTLA4Ig could partially inhibit antigen-specific (tuberculin) and polyclonal (anti-CD3) lymphoproliferation and interferon-gamma (IFN-gamma) secretion of T cells cocultured with autologous monocytes. IFN-gamma secretion was more sensitive to blocking costimulation than proliferation. The antibody BB-1 did not inhibit proliferation and cytokine secretion, nor did the anti-CD86 clone IT2.2. CTLA4Ig, which binds both CD80 and CD86, has the same inhibitory capacity as the anti-CD80 antibody tested. From those findings we conclude that human monocytes use CD80 as a costimulatory ligand for CD28 and utilize other costimulatory mechanisms besides those mediated via molecules of the B7 family.
Fleischer
J
J
Forschungszentrum Borstel, Department of Immunology and Cell Biology, Germany.
Soeth
E
E
Reiling
N
N
Grage-Griebenow
E
E
Flad
H D
HD
Ernst
M
M
D015703:Antigens, CD / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D018122:B7-1 Antigen / Q000032:analysis / Q000235:genetics / Q000276:immunology; D051940:B7-2 Antigen; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology; D014373:Tuberculin / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D017252:CD3 Complex; C497964:CD86 protein, human; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D014373:Tuberculin; D007371:Interferon-gamma