Document 0792
 DOCN  M95A0792
 TI    Murine Th1 and Th2 cell clones differentially regulate macrophage nitric
       oxide production.
 DT    9510
 AU    Taub DD; Cox GW; Clinical Services Program, Program Resources, Inc.,
       DynCorp,; Frederick, Maryland 21702, USA.
 SO    J Leukoc Biol. 1995 Jul;58(1):80-9. Unique Identifier : AIDSLINE
       MED/95341178
 AB    Previous studies have demonstrated that the combination of the T helper
       cell 1 (Th1)-derived cytokines interleukin (IL)-2 and interferon
       (IFN)-gamma induces nitric oxide (NO) production and tumor cytolysis by
       mouse peritoneal macrophages and the mouse macrophage cell line ANA-1 in
       vitro. Conversely, the Th2-derived cytokine IL-4 inhibits IL-2 and
       IFN-gamma-induced NO production and tumor cytolysis by ANA-1
       macrophages. To examine the paracrine regulatory effects of Th1 and Th2
       cells on macrophages, various mouse T cell clones were tested for their
       ability to regulate NO production by mouse peritoneal macrophages or
       ANA-1 macrophages. Antigen, superantigen, and mitogen stimulated Th1
       cells but not Th2 cells induced NO production by macrophages.
       Supernatants from these activated Th1 clones also induced NO production
       by peritoneal macrophages and ANA-1 macrophages. Neutralization analysis
       using monoclonal anticytokine antibodies revealed that both IL-2 and
       IFN-gamma production by activated Th1 cells were required for the
       production of NO by macrophages. Co-culture studies using a panel of Th2
       cell clones that share the same antigen specificity revealed that these
       cells suppressed Th1-mediated macrophage activation. The Th2-mediated
       impairment of Th1-induced NO production was primarily due to the
       secretion of IL-4. IL-4 appeared to have a direct effect on macrophage
       activation because neither mitogen-induced proliferation of Th1 cells
       nor cytokine production by Th1 cells were affected by IL-4. Overall,
       these results suggest that a potent paracrine regulatory network
       involving Th1 cells and Th2 cells may control the activation of
       macrophages for NO production and antitumor cytotoxicity.
 DE    Animal  Cell Line  Clone Cells  Cytokines/SECRETION  In Vitro
       Interleukin-4/PHARMACOLOGY  Lymphocyte Transformation  *Macrophage
       Activation  Macrophages, Peritoneal/*METABOLISM  Mice  Mice, Inbred BALB
       C  Mice, Inbred C3H  Nitric Oxide/*BIOSYNTHESIS
       Superantigens/IMMUNOLOGY  Th1 Cells/*PHYSIOLOGY  Th2 Cells/*PHYSIOLOGY
       Tumor Necrosis Factor/BIOSYNTHESIS  JOURNAL ARTICLE

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