       Document 0082
 DOCN  M9640082
 TI    Down-regulation of T lymphocyte activation in vitro and in vivo induced
       by glycoinositolphospholipids from Trypanosoma cruzi. Assignment of the
       T cell-suppressive determinant to the ceramide domain.
 DT    9604
 AU    Gomes NA; Previato JO; Zingales B; Mendonca-Previato L; DosReis GA;
       Institute of Microbiology, Federal University of Rio de Janeiro,;
       Brazil.
 SO    J Immunol. 1996 Jan 15;156(2):628-35. Unique Identifier : AIDSLINE
       MED/96132989
 AB    The major surface glycoinositolphospholipid (GIPL) from Trypanosoma
       cruzi was purified and assessed in mouse T cell function assays.
       Purified GIPLs from T. cruzi strains Y and G, but not from a plant
       trypanosomatid (Phytomonas serpens), markedly blocked in vitro CD4+ and
       CD8+ T cell mitogenesis induced by bacterial superantigen and
       anti-TCR;CD3 Abs. Secretion of IL-2, but not of IL-4, bioactivity, was
       reduced by GIPLs. T. cruzi, but not P. serpens, GIPL also blocked recall
       cellular responses to T. cruiz. GIPLs from T. cruzi, but not from P.
       serpens, blocked in vivo regional lymph node T cell activation induced
       by anti-CD3 mAb. Blockage led to loss of IL-2 responsiveness, with
       inhibition of CD25 expression on both CD4+ and CD8+ subsets. Isolated
       phosphoinositol oligosaccharides from GIPLs had no effect on in vitro
       CD4+ T cell mitogenesis. Isolated ceramide from T. cruzi GIPLs contained
       mainly N-lignoceroyldihydrosphingosine and blocked CD4+ T cell
       activation in vitro with the same potency as the intact GIPL. Standard
       N-palmitoylsphingosine, but not N-palmitoyldihydrosphingosine, blocked
       CD4+ T cell mitogenesis. A longer fatty acid chain, such as in standard
       N-lignoceroyldihydrosphingosine, or in the natural trypanosomal
       GIPL-derived ceramide, however, conferred full inhibitory effects on
       CD4+ T cells. These results demonstrate that T. cruzi GIPL has T cell
       immunomodulatory activity in vitro and in vivo, and that this novel
       activity maps to the ceramide domain. These findings could have
       implications for immunologic disturbances induced in the host by the
       causative agent of Chagas' disease.
 DE    Animal  Antigens, Bacterial/IMMUNOLOGY  Carbohydrate Sequence
       Carbohydrates/ISOLATION & PURIF  Ceramides/CHEMISTRY/ISOLATION &
       PURIF/PHYSIOLOGY  Chagas Disease/IMMUNOLOGY  Comparative Study
       CD4-Positive T-Lymphocytes/DRUG EFFECTS/IMMUNOLOGY  CD8-Positive
       T-Lymphocytes/DRUG EFFECTS/IMMUNOLOGY  Depression, Chemical
       Enterotoxins/IMMUNOLOGY  Female
       Glycosylphosphatidylinositols/CHEMISTRY/ISOLATION & PURIF/
       *PHARMACOLOGY  Interleukins/BIOSYNTHESIS  Lipids/ISOLATION & PURIF
       Lymph Nodes/CYTOLOGY  Lymphocyte Transformation/*DRUG EFFECTS  Male
       Mice  Muromonab-CD3/PHARMACOLOGY  Nuclear Magnetic Resonance
       Receptor-CD3 Complex, Antigen, T-Cell/ANTAGONISTS & INHIB  Signal
       Transduction/DRUG EFFECTS  Superantigens/IMMUNOLOGY  Support, Non-U.S.
       Gov't  T-Lymphocyte Subsets/*DRUG EFFECTS/IMMUNOLOGY  Trypanosoma
       cruzi/*CHEMISTRY/IMMUNOLOGY  Trypanosomatina/CHEMISTRY  JOURNAL ARTICLE

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

