Abstract
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 (MΦ) 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-1+2+ population which comprised up to 20% of the splenocytes in tumor-bearers (TB), but is negligible in spleens from normal mice. These Mac-1+2+ MΦ 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 MΦ, T cell responses were relatively refractory to PGE2-mediated down-regulation. Instead, they were suppressed by a contact-dependent T cell-MΦ interaction. Furthermore, tumor-derived factors such as granulocyte-MΦ colony-stimulating factor (GM-CSF) seem to play an important role in the induction and expansion of the Mac-1+2+ MΦ. These cells appear to mediate down-regulation of the host immune responses by at least two distinct mechanisms: 1) PGE2 production and 2) a cell contact-dependent, but non-major-histocompatibility-complex-specific, interaction.
Original language | English (US) |
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Pages (from-to) | 126-138 |
Number of pages | 13 |
Journal | Journal of Leukocyte Biology |
Volume | 49 |
Issue number | 2 |
DOIs | |
State | Published - 1991 |
Keywords
- GM-CSF
- down-regulation
- mixed leukocyte culture
- prostaglandin E
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Cell Biology