Distinctive maturation of in vitro versus in vivo anti-CD40 mAb-matured dendritic cells in mice

Dendritic cells (DCs) can be matured by CD40 stimulation to upregulate their MHC class II/peptide complexes and costimulatory molecule surface expression to become adept at presenting antigen to and activating naive T lymphocytes. The use of anti-CD40 antibodies as adjuvants for DC-based therapy has been advanced. Little is known as to how DC biology in response to CD40 ligation differs between in vitro versus in vivo ligation. Therefore, the authors analyzed the expression kinetics of MHC class II(I-A(k))[HEL peptide "complex," total MHC class II, CD80, and CD86 on in vitro or in vivo CD40-stimulated DCs over a period of 5 days. MHC class II, "complex," and costimulatory molecule expression was elevated at 1 day in vitro and stayed high for the culture period, whereas in vivo expression of the cohort of molecules peaked earlier and then declined. When purified DCs were co-cultured in vitro with antigen-specific T cell hybridomas, the DCs had lower expression of total MHC class II and "complex," but did not reduce their CD80 and CD86 expression. The lower expression was dependent on cognate interaction as a non-antigen-specific T cell hybridoma was without effect. Blocking antigen-specific MHC class II/peptide-T cell receptor (TcR) complex interaction with antibody inhibited the reduction of MHC class II expression on CD40-stimulated DCs in vitro. Overall, their studies suggest distinct response of DCs to typical conditions that feature anti-CD40 monoclonal antibody(mAb)-activated DCs in vitro or in vivo.