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

G. A. Watson, Y. X. Fu, D. M. Lopez

Research output: Contribution to journalArticle

61 Scopus citations

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 languageEnglish (US)
Pages (from-to)126-138
Number of pages13
JournalJournal of Leukocyte Biology
Volume49
Issue number2
DOIs
StatePublished - Jan 1 1991

Keywords

  • GM-CSF
  • down-regulation
  • mixed leukocyte culture
  • prostaglandin E

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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