Document 0189
 DOCN  M95A0189
 TI    Th1 and Th2 T-helper cells exert opposite regulatory effects on
       procoagulant activity and tissue factor production by human monocytes.
 DT    9510
 AU    Del Prete G; De Carli M; Lammel RM; D'Elios MM; Daniel KC; Giusti B;
       Abbate R; Romagnani S; Division of Clinical Immunology and Allergology,
       Istituto di; Clinica Medica 3, Florence, Italy.
 SO    Blood. 1995 Jul 1;86(1):250-7. Unique Identifier : AIDSLINE MED/95315544
 AB    The role of T-cell subsets in the induction of tissue factor (TF)
       production by human monocytes in vitro was investigated. Mitogen
       stimulation enabled both unfractionated T cells and their CD4+ or CD8+
       subsets to promote procoagulant activity (PCA). After mitogen or antigen
       activation, all seven T-cell clones with Th1 cytokine profile, but none
       of seven Th2 clones, induced TF production and PCA. T-cell blasts from
       four Th1 activated clones were fixed with paraformaldehyde and added to
       monocytes in the presence of medium alone or their supernatants.
       Addition of either fixed Th1 cells or their supernatants induced low TF
       production (0.2 to 0.6 ng/mL), whereas addition of both resulted in much
       higher TF synthesis (1.8 to 3.4 ng/mL). Among Th1-type cytokines, only
       interferon-gamma (IFN-gamma) induced minimal TF production (0.1 to 0.4
       ng/mL). No TF synthesis was induced by activated and fixed Th2 cells
       and/or their supernatants, whereas combined addition of fixed Th2 cells
       and Th1 supernatants or IFN-gamma induced noticeable TF production. The
       addition of either anti-IFN-gamma antibody or Th2 supernatants to
       monocytes stimulated with activated and fixed Th1 cells plus their
       supernatant resulted in a dose-dependent inhibition of TF synthesis,
       which was partially restored by neutralization of interleukin-4 (IL-4)
       or IL-10. Addition of recombinant IL-4, IL-13, or IL-10, but not IL-5,
       inhibited the Th1-induced TF production by monocytes. Data indicate that
       both CD8+ and CD4+ Th1, but not Th2, T cells can help TF production and
       PCA. Both cell-to-cell contact with activated T cells and Th1-type
       cytokines, in particular IFN-gamma, are required for optimal TF
       synthesis, whereas Th2-derived cytokines (IL-4, IL-13, and IL-10) are
       inhibitory. This may be of potential interest for future therapeutic
       strategies.
 DE    Antigens/IMMUNOLOGY  Blood Coagulation Factors/*BIOSYNTHESIS/GENETICS
       Cell Communication  Comparative Study
       Cytokines/PHARMACOLOGY/*PHYSIOLOGY  CD8-Positive
       T-Lymphocytes/IMMUNOLOGY/SECRETION  *Gene Expression Regulation/DRUG
       EFFECTS  Human  Interferon Type II/PHARMACOLOGY/*PHYSIOLOGY
       Interleukins/PHARMACOLOGY/PHYSIOLOGY  Leukocytes, Mononuclear/DRUG
       EFFECTS/*METABOLISM  Lymphocyte Transformation  Recombinant
       Proteins/PHARMACOLOGY  Support, Non-U.S. Gov't
       Thromboplastin/*BIOSYNTHESIS/GENETICS  Th1 Cells/*PHYSIOLOGY  Th2
       Cells/*PHYSIOLOGY  JOURNAL ARTICLE

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