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1994-08-27
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Document 0776
DOCN M9480776
TI Cytochalasin D modulates CD4 crosslinking sensitive mitogenic signal in
T lymphocytes.
DT 9410
AU Aszalos A; Pine PS; Weaver JL; Rao PE; Center for Drug Evaluations and
Research, FDA, Washington, DC; 20204.
SO Cell Immunol. 1994 Aug;157(1):81-91. Unique Identifier : AIDSLINE
MED/94313697
AB It has previously been shown that crosslinking of the CD4 molecule,
either with anti-Leu3a mAb or with gp120 (the HIV coat protein) plus
anti-gp120 mAb, suppresses activation induced by wt31, a
TcR/CD3-specific mAb. This suppression was associated with hindrance of
the necessary association of the p56lck kinase bearing CD4 molecule with
the TcR/CD3 complex. In this paper we demonstrate that this
crosslinking-induced suppression can be bypassed by perturbing the
microfilament system of CD4+ cells by pretreatment with 1 microM
cytochalasin D. Using the fluorescence resonance energy transfer method,
we have shown that the cytochalasin D-affected increase of mitogenesis
is not due to changes in the TcR/CD3 to CD4 distance. Likewise, other
membrane biophysical parameters, membrane potential and lateral
diffusion of surface receptors, cannot be associated with these
cytochalasin D-affected mitogenic changes. Cytochalasin D treatment
elevates intracellular Ca2+ levels induced by wt31 mAb plus crosslinking
and generates a TcR/CD3-dependent signal which is cyclosporin sensitive.
DE Antibodies, Monoclonal Antigens, CD4/*PHYSIOLOGY Calcium/*PHYSIOLOGY
Cyclosporine/PHARMACOLOGY Cytochalasin D/*PHARMACOLOGY Flow Cytometry
Fluorescence Human Lymphocyte Transformation/DRUG EFFECTS Membrane
Potentials/DRUG EFFECTS/PHYSIOLOGY Photochemistry Receptor-CD3
Complex, Antigen, T-Cell/DRUG EFFECTS/PHYSIOLOGY Receptors,
Interleukin-2/IMMUNOLOGY Signal Transduction/DRUG EFFECTS/*IMMUNOLOGY
T4 Lymphocytes/DRUG EFFECTS/*PHYSIOLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).