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 Citations (Scopus)

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
StatePublished - Apr 9 1991

Fingerprint

Macrophages
Antigens
Dinoprostone
Down-Regulation
Neoplasms
T-Lymphocytes
B-Lymphocytes
9,10-Dimethyl-1,2-benzanthracene
Granulocyte Colony-Stimulating Factor
Tumor Burden
Major Histocompatibility Complex
Cell Communication
Population
Immune System
Adenocarcinoma
Breast
Spleen
Monoclonal Antibodies
U 78517F
Staining and Labeling

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Splenic macrophages from tumor-bearing mice co-expressing MAC-1 and MAC-2 antigens exert immunoregulatory functions via two distinct mechanisms. / Watson, G. A.; Fu, Y. X.; Lopez, D. M.

In: Journal of Leukocyte Biology, Vol. 49, No. 2, 09.04.1991, p. 126-138.

Research output: Contribution to journalArticle

@article{d6d052d2e58c497cb7b5cf3d75d2cfd4,
title = "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 (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.",
keywords = "down-regulation, GM-CSF, mixed leukocyte culture, prostaglandin E",
author = "Watson, {G. A.} and Fu, {Y. X.} and Lopez, {D. M.}",
year = "1991",
month = "4",
day = "9",
language = "English (US)",
volume = "49",
pages = "126--138",
journal = "Journal of Leukocyte Biology",
issn = "0741-5400",
publisher = "FASEB",
number = "2",

}

TY - JOUR

T1 - Splenic macrophages from tumor-bearing mice co-expressing MAC-1 and MAC-2 antigens exert immunoregulatory functions via two distinct mechanisms

AU - Watson, G. A.

AU - Fu, Y. X.

AU - Lopez, D. M.

PY - 1991/4/9

Y1 - 1991/4/9

N2 - 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.

AB - 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.

KW - down-regulation

KW - GM-CSF

KW - mixed leukocyte culture

KW - prostaglandin E

UR - http://www.scopus.com/inward/record.url?scp=0025804994&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025804994&partnerID=8YFLogxK

M3 - Article

C2 - 1991996

AN - SCOPUS:0025804994

VL - 49

SP - 126

EP - 138

JO - Journal of Leukocyte Biology

JF - Journal of Leukocyte Biology

SN - 0741-5400

IS - 2

ER -