B70/B7-2 is identical to CD86 and is the major functional ligand for CD28 expressed on human dendritic cells.
Dendritic cells comprise a system of highly efficient antigen-presenting cells involved in the initiation of T cell responses. Herein, we investigated the role of the CD28 pathway during alloreactive T cell proliferation induced by dendritic-Langerhans cells (D-Lc) generated by culturing human cord blood CD34+ progenitor cells with granulocyte/macrophage colony-stimulating factor and tumor necrosis factor alpha. In addition to expressing CD80 (B7/BB1), a subset of D-Lc expressed B70/B7-2. Binding of the CTLA4-Ig fusion protein was completely inhibited by a combination of monoclonal antibodies (mAbs) against CD80 and B70/B7-2, indicating the absence of expression of a third ligand for CD28/CTLA-4. It is interesting to note that mAbs against CD86 completely prevented the binding of CTLA4-Ig in the presence of mAbs against CD80 and bound to a B70/B7-2-transfected fibroblast cell line, demonstrating that the B70/B7-2 antigen is identical to CD86. CD28 triggering was essential during D-Lc-induced alloreaction as it was inhibited by mAbs against CD28 (9 out of 11 tested). However, none of six anti-CD80 mAbs demonstrated any activity on the D-Lc-induced alloreaction, though some were previously described as inhibitory in assays using CD80-transfected cell lines. In contrast, a mAb against CD86 (IT-2) was found to suppress the D-Lc-dependent alloreaction by 70%. This inhibitory effect was enhanced to > or = 90% when a combination of anti-CD80 and anti-CD86 mAbs was used. The present results demonstrate that D-Lc express, in addition to CD80, the other ligand for CTLA-4, CD86 (B70/B7-2), which plays a primordial role during D-Lc-induced alloreaction.
Caux
C
C
Laboratory for Immunological Research, Schering-Plough, Dardilly, France.
Vanbervliet
B
B
Massacrier
C
C
Azuma
M
M
Okumura
K
K
Lanier
L L
LL
Banchereau
J
J
D000069594:Abatacept; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000378:metabolism*; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology*; D006801:Humans; D018796:Immunoconjugates; D008562:Membrane Glycoproteins / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D000069594:Abatacept