ROLE OF MACROPHAGES AND DENDRITIC CELLS IN PRIMARY CYTOTOXIC T-LYMPHOCYTE RESPONSES

The successful induction of class I restricted cytotoxic T lymphocytes (CTL) responses with soluble non-replicating antigens relies upon veh icles which deliver antigen in vivo appropriately to antigen presentin g cells (APC), which for CTL may be dendritic cells (DC). In this stud y, we have followed the distribution of liposomes and their incorporat ed antigen and compared the efficacy of splenic macrophages (Me) and D C at inducing primary CTL responses in vitro. Our results show that wh ereas liposomes locate predominantly in the splenic red pulp and margi nal zone locations, some of their soluble antigen contents redistribut e to the central white pulp, comprising mainly DC and T cells. Such an tigen redistribution was most apparent following administration of pH- sensitive liposomes. In comparisons of the APC activity of MB and DC t aken at various times post-injection, DC were always superior to Mo. H owever, if Mo were depleted prior to antigen exposure, DC were ineffec tive APC for CTL induction. Furthermore, addition of supernatant from OVA-liposome treated Mo to naive DC-T cell cultures in vitro resulted in OVA-specific T cell responses. These studies indicate a role for Mo in enhancing the antigen presenting function of DC.