Th1 CD4+ lymphocytes delete activated macrophages through the Fas/APO-1 antigen pathway Journal Article

Authors: Ashany, D.; Song, X.; Lacy, E.; Nikolic-Zugic, J.; Friedman, S. M.; Elkon, K. B.
Article Title: Th1 CD4+ lymphocytes delete activated macrophages through the Fas/APO-1 antigen pathway
Abstract: The Fas/APO-1 cytotoxic pathway plays an important role in the regulation of peripheral immunity. Recent evidence indicates that this regulatory function operates through deletion of activated T and B lymphocytes by CD4+ T cells expressing the Fas ligand. Because macrophages play a key role in peripheral immunity, we asked whether Fas was involved in T-cell-macrophage interactions. Two-color flow cytometry revealed that Fas receptor (FasR) was expressed on resting murine peritoneal macrophages. FasR expression was upregulated after activation of macrophages with cytokines or lipopolysaccharide, although only tumor necrosis factor-α rendered macrophages sensitive to anti-FasR antibody-mediated death. To determine the consequence of antigen presentation by macrophages to CD4+ T cells, macrophages were pulsed with antigen and then incubated with either Th1 or Th2 cell lines or clones. Th1, but not Th2, T cells induced lysis of 60-80% of normal macrophages, whereas macrophages obtained from mice with mutations in the FasR were totally resistant to Th1-mediated cytotoxicity. Macrophage cytotoxicity depended upon specific antigen recognition by T cells and was major histocompatibility complex restricted. These findings indicate that, in addition to deletion of activated lymphocytes, Fas plays an important role in deletion of activated macrophages after antigen presentation to Th1 CD4+ T cells. Failure to delete macrophages that constitutively present self- antigens may contribute to the expression of autoimmunity in mice deficient in FasR (lpr) or Fas ligand (gld).
Keywords: controlled study; human cell; nonhuman; animal cell; mouse; animal; mice; cell death; apoptosis; mice, mutant strains; mice, inbred balb c; animalia; antigen presentation; antigen recognition; cytotoxic t lymphocyte; murinae; perforin; autoimmunity; cytotoxicity, immunologic; cd4 antigen; mice, inbred cba; macrophages; major histocompatibility complex; antigen-presenting cells; receptors, cell surface; mice, inbred c3h; immunity, cellular; th2 cells; th1 cells; macrophage activation; antigens, cd95; peritoneum macrophage; b lymphocyte activation; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 92
Issue: 24
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 1995-11-21
Start Page: 11225
End Page: 11229
Language: English
DOI: 10.1073/pnas.92.24.11225
PUBMED: 7479970
PROVIDER: scopus
Notes: Article -- Export Date: 28 August 2018 -- Source: Scopus
Citation Impact
MSK Authors
  1. Elizabeth H Lacy
    70 Lacy