       Document 0226
 DOCN  M9620226
 TI    Th1 CD4+ lymphocytes delete activated macrophages through the Fas/APO-1
       antigen pathway.
 DT    9602
 AU    Ashany D; Song X; Lacy E; Nikolic-Zugic J; Friedman SM; Elkon KB;
       Specialized Center of Research in Systemic Lupus Erythematosus,;
       Hospital for Special Surgery-Cornell University Medical Center,; New
       York, NY 10021, USA.
 SO    Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11225-9. Unique Identifier
       : AIDSLINE MED/96074680
 AB    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-alpha 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).
 DE    Animal  Antigen-Presenting Cells/CYTOLOGY  Antigens, CD95/*PHYSIOLOGY
       Cell Death  Cytotoxicity, Immunologic  Immunity, Cellular  Macrophage
       Activation  Macrophages/*CYTOLOGY  Major Histocompatibility Complex
       Mice  Mice, Inbred BALB C  Mice, Inbred CBA  Mice, Inbred C3H  Mice,
       Mutant Strains  Receptors, Cell Surface/PHYSIOLOGY  Support, Non-U.S.
       Gov't  Support, U.S. Gov't, P.H.S.  Th1 Cells/CYTOLOGY/*IMMUNOLOGY  Th2
       Cells/IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

