Document 1148
 DOCN  M9591148
 TI    Activation of CD4+ T cells in the presence of a nondepleting monoclonal
       antibody to CD4 induces a Th2-type response in vitro.
 DT    9509
 AU    Stumbles P; Mason D; Medical Research Council Cellular Immunology Unit,
       Sir William; Dunn School of Pathology, University of Oxford, United
       Kingdom.
 SO    J Exp Med. 1995 Jul 1;182(1):5-13. Unique Identifier : AIDSLINE
       MED/95310864
 AB    In vitro experiments using purified rat CD4+ T cells in primary and
       secondary mixed leukocyte cultures (MLC) have been carried out to
       explore the mechanism of inhibition of cell-mediated autoimmune disease
       in the rat by a nondepleting monoclonal antibody (mAb) to CD4. Previous
       work has shown that W3/25, a mouse anti-rat CD4 mAb of immunoglobulin G1
       isotype, completely prevents the development of the paralysis associated
       with experimental allergic encephalomyelitis (EAE) in Lewis rats, but
       does so without eliminating the encephalitogenic T cells. The in vitro
       experiments described in this study have shown that when CD4+ T cells
       were activated in the presence of the anti-CD4 mAb in a primary MLC, the
       synthesis of interferon (IFN) gamma, but not interleukin (IL) 2, was
       completely inhibited. After secondary stimulation, now in the absence of
       the mAb, the synthesis of IL-4 and IL-13 mRNA was greatly enhanced
       compared with that observed from CD4+ T cells derived from primary
       cultures in which the mAb was omitted. As IL-4 and IL-13 are known to
       antagonize cell-mediated immune reactions, and as EAE is cell-mediated
       disease, the data suggest that the W3/25 mAb controls EAE by modifying
       the cytokine repertoire of T cells that respond to the encephalitogen.
       The capacity for the mAb to suppress IFN-gamma synthesis provides, in
       part, an explanation for this change in cytokine production. These
       findings are discussed in terms of what is known of the factors that
       determine which cytokine genes are expressed on T cell activation.
       Possible implications for the evolution of T cell responses in human
       immunodeficiency virus infection are also discussed.
 DE    Animal  Antibodies, Monoclonal/*IMMUNOLOGY  Antigens, CD4/*IMMUNOLOGY
       Base Sequence  Cells, Cultured  CD4-Positive T-Lymphocytes/*IMMUNOLOGY
       Gene Expression Regulation  Interferon Type II/BIOSYNTHESIS/GENETICS
       Interleukin-13/BIOSYNTHESIS/GENETICS
       Interleukin-2/BIOSYNTHESIS/GENETICS
       Interleukin-4/BIOSYNTHESIS/GENETICS/PHARMACOLOGY  Lymphocyte Culture
       Test, Mixed  *Lymphocyte Transformation  Male  Molecular Sequence Data
       Rats  Rats, Inbred Strains  Specific Pathogen-Free Organisms  Support,
       Non-U.S. Gov't  Th2 Cells/*IMMUNOLOGY  JOURNAL ARTICLE

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