THE IMMUNE-RESPONSE INDUCED IN-VIVO BY DENDRITIC CELLS IS DEPENDENT ON B7-1 OR B7-2, BUT THE INHIBITION OF BOTH SIGNALS DOES NOT LEAD TO TOLERANCE

Dendritic cells (DC) can be used as physiological adjuvant in vivo, In deed, a single injection of DC, pulsed in vitro with antigen, induces activation of specific T and B lymphocytes in syngeneic mice, The uniq ue capacity of DC to sensitize naive T lymphocytes correlates with ele vated expression of MHC antigens as well as co-stimulatory molecules, The aim of this work was to evaluate the functional role of the indivi dual CD28 ligands in the induction of primary humoral and cellular res ponses, and to characterize the nature of the immune response induced in the presence of selected co-stimulatory molecules, Our data show th at the primary response is strictly B7 dependent, and that B7-1 and B7 -2 mediate overlapping co-stimulatory functions, as either molecule al one is sufficient to initiate an immune reaction, Inhibition of B7-1 a nd B7-2, however, does not lead to tolerance as predicted by the two-s ignal hypothesis, Rather, recognition of antigen in the absence of B7 appears as a null event, since subsequent immunogenic stimulation resu lts in a primary response, Blockade of B7-2 co-stimulatory molecules s ignificantly inhibits antigen-specific IgG1 but not IgG2a production, suggesting that B7-2 may direct the development of T(h)2 cells, These data emphasize the critical role of the CD28/B7 pathway in the inducti on of the immune response by DC, which appear to be the initiating ant igen-presenting cells in situ.