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M9630253.TXT
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1996-02-27
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Document 0253
DOCN M9630253
TI Costimulation of CD3/TcR complex with either integrin or nonintegrin
ligands protects CD4+ allergen-specific T-cell clones from programmed
cell death.
DT 9603
AU Agea E; Bistoni O; Bini P; Migliorati G; Nicoletti I; Bassotti G;
Riccardi C; Bertotto A; Spinozzi F; Department of Internal Medicine,
University of Perugia, Italy.
SO Allergy. 1995 Aug;50(8):677-82. Unique Identifier : AIDSLINE
MED/96098155
AB An optimal stimulation of CD4+ cells in an immune response requires not
only signals transduced via the TcR/CD3 complex, but also costimulatory
signals delivered as a consequence of interactions between T-cell
surface-associated costimulatory receptors and their counterparts on
antigen-presenting cells (APC). The intercellular adhesion molecule-1
(ICAM-1, CD54) efficiently costimulates proliferation of resting, but
not antigen-specific, T cells. In contrast, CD28 and CD2 support
interleukin (IL)-2 synthesis and proliferation of antigen-specific T
cells more efficiently than those of resting T cells. The molecular
basis for this differential costimulation of T cells is poorly
understood. Cypress-specific T-cell clones (TCC) were generated from
four allergic subjects during in vivo seasonal exposure to the allergen.
Purified cypress extract was produced directly from fresh collected
pollen and incubated with the patients' mononuclear cells. Repeated
allergen stimulation was performed in T-cell cultures supplemented with
purified extract and autologous APC. The limiting-dilution technique was
then adopted to generate allergen-specific TCC, which were also
characterized by their cytokine secretion pattern as Th0 (IL-4 plus
interferon-gamma) or Th2 (IL-4). Costimulation-induced proliferation or
apoptosis was measured by propidium iodide cytofluorometric assay. By
cross-linking cypress-specific CD4+ and CD8+ T-cell clones with either
anti-CD3 or anti-CD2, anti-CD28, and anti-CD54 monoclonal antibodies, we
demonstrated that CD4+ clones (with Th0- or Th2-type cytokine production
pattern) undergo programmed cell death only after anti-CD3 stimulation,
whereas costimulation with either anti-CD54 or anti-CD28 protects target
cells from apoptosis.(ABSTRACT TRUNCATED AT 250 WORDS)
DE Allergens/*IMMUNOLOGY Antigen-Presenting Cells/IMMUNOLOGY Antigens,
CD2/IMMUNOLOGY Antigens, CD28/IMMUNOLOGY Antigens, CD3/*IMMUNOLOGY
Apoptosis/*PHYSIOLOGY Cell Division Cells, Cultured Clone Cells
CD4-Positive T-Lymphocytes/*IMMUNOLOGY CD8-Positive
T-Lymphocytes/*IMMUNOLOGY Hay Fever/IMMUNOLOGY Human
Integrins/*IMMUNOLOGY Intercellular Adhesion Molecule-1/IMMUNOLOGY
Interleukin-1/METABOLISM Pollen/IMMUNOLOGY Receptors, Antigen,
T-Cell/*IMMUNOLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).