Splenic Macrophages From Tumor-Bearing Mice Co-Expressing MAC-1 and MAC-2 Antigens Exert Immunoregulatory Functions Via Two Distinct Mechanisms

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 (M phi) 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+ M phi 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 M phi, T cell responses were relatively refractory to PGE2-mediated down-regulation. Instead, they were suppressed by a contact-dependent T cell-M phi interaction. Furthermore, tumor-derived factors such as granulocyte-M phi colony-stimulating factor (GM-CSF) seem to play an important role in the induction and expansion of the Mac-1+2+ M phi. 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.

Comparative effects of Mycobacterium avium glycopeptidolipid and lipopeptide fragment on the function and ultrastructure of mononuclear cells

“…Watson ft til. [35] have shown that murine macrophages infected with Myco. tubercuhisis predominantly express Mac-2 antigens in comparison with macrophages from normal mice.…”

STAT1 Signaling Regulates Tumor-Associated Macrophage-Mediated T Cell Deletion

“…The presence of immunosuppressive myeloid cell in spleens of tumor-bearing mice is well-established phenomenon first described almost three decades ago (1,2). These cells share common features such as myeloid origin, macrophage-like morphology, and phenotype of surface receptors, and the ability to suppress CD4 ϩ and CD8 ϩ T cells after culture in vitro (3)(4)(5)(6)(7)(8)(9). Initial studies have been focused on immunosuppressive activity of macrophages.…”

“…Initial studies have been focused on immunosuppressive activity of macrophages. More recently, the population of immature myeloid cells (IMC) 3 in spleens of tumor-bearing mice was more precisely identified as Gr-1 ϩ CD11b ϩ cells (reviewed in Refs. 10 and 11).…”

Impaired thymopoiesis occurring during the thymic involution of tumor-bearing mice is associated with a down-regulation of the antiapoptotic proteins Bcl-XL and A1

“…For instance, some pro-apoptotic members of the Bcl-2 family such as Bax have been shown to heterodimerize with Bcl-X L and A1 (60,62). Previously, we have reported that the mammary tumor cells used in our studies secrete several factors that have effects in various compartments of the immune system (63)(64)(65)(66)(67). It could be argued that an impaired function of the stromal cell microenvironment could induce the expression of some pro-apoptotic proteins as a result of these tumor-associated factors, interact with the anti-apoptotic counterpart and cause the alterations observed in thymocyte differentiation and thymic morphogenesis.…”