Splenic macrophages from tumor-bearing mice co-expressing Mac-1 and Mac-2 antigens exert immunoregulatory functions via two distinct mechanisms

Tumor burden has been shown to induce a variety of phenotypic and functional changes in the cellular constituents of the host’s immune system. These changes have been implicated as mechanisms by which tumors avoid rejection. Studies of BALB/c mice bearing a D1-DMBA-3 mammary adenocarcinoma showed alterations of the splenocyte populations. There was a five-fold increase of macrophages (M4)that were phenotypically and functionally analyzed to establish their role in tumor-induced modifications of the host’s immune response. Monoclonal antibody staining defined a Mac-i population which comprised up to 20 % of the splenocytes in tumor-bearers (TB), but is negligible in spleens from normal mice. These Mac-i M4 were found to mediate down-regulation of both polyclonal and antigen-specific T and B cell responses in vitro and in vivo. Although B cell responses were suppressed via prostaglandin E2 (PGE2) production by the TB M4, T cell responses were relatively refractory to PGE2-mediated down-regulation. Instead, they were suppressed by a contact-dependent T cell-M4 interaction. Further-more, tumor-derived factors such as granulocyte-M4 colony-stimulating factor (GM-CSF) seem to play an Important role in the induction and expansion of the Mac-i M4. These cells appear to mediate down-regulation of the host immune responses by at least two distinct mechanisms: i) PGE2 production and 2) a cell contact-dependent, but non-major-histocompatibility-complex-specific, interaction. Key words: prostaglandin E2, mixed leukocyte culture, down-regulation, GM-CS