Induction of dendritic cell costimulator molecule expression is suppressedby T cells in the absence of antigen-specific signalling: role of cluster formation, CD40 and HLA-class II for dendritic cell activation

Full activation of T lymphocytes by dendritic cells (DC) during antigen pre sentation is known to require the interaction of several inducible receptor -ligand pairs. We have postulated that the reciprocal activation of DC by T lymphocytes is also important. Potential signalling molecules that might i ncrease the stimulatory capacity of DC during antigen presentation to T lym phocytes were tested using an in vitro model. Fresh human blood DC were coc ultured with CD4(+) and CD8(+) allogeneic or with autologous T lymphocytes plus Staphylococcus superantigen A (SEA). Surprisingly, costimulator expres sion on DC cocultured with T lymphocytes was reduced in comparison to DC cu ltured alone. However, the minority (10-30%) of DC clustering with T lympho cytes showed antigen-specific up-regulation of the CD40, CD80 and CD86 cost imulator molecules, whereas the non-clustered DC (70-90%) had less up-regul ation than control DC cultured alone and did not respond to antigen-specifi c triggering. Monoclonal antibodies (mAb) to CD40 ligand (CD40L) and human leucocyte antigen (HLA)-DR, but not lymphocyte function-associated antigen- 1 (LFA-1), LFA-3 or HLA-class I, significantly inhibited the T-lymphocyte i nduction of DC costimulator expression. Since HLA-class II, but not HLA-cla ss I mAb, inhibited allogeneic T-lymphocyte-mediated activation of DC, CD4 T lymphocytes appear to be the main subset activating DC in the mixed lymph ocyte reaction. Cross-linking of CD40, but not HLA-class II, up-regulated D C or B-cell costimulator expression. Although direct class II signalling do es not appear to play a role in DC activation, antigen-specific T-cel recog nition contributes via other mechanisms to regulate DC activation.