Document 2777
 DOCN  M94A2777
 TI    Selective inhibition of CTL against CD4S.
 DT    9412
 AU    Grant M; Gomez A; Smaill F; Muller S; Kohler H; Rosenthal K; Immune
       Network Research, Vancouver, Canada.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):227 (abstract no. PB0336). Unique
       Identifier : AIDSLINE ICA10/94369798
 AB    Human Immunodeficiency Virus (HIV)-infected individuals have CD8+
       cytotoxic T lymphocytes (CTL) that kill uninfected CD4+ lymphocytes in
       vitro. These CTL are specific for CD4+ lymphocytes and have been
       associated with rapid CD4 depletion in vivo. CTL against uninfected CD4+
       lymphocytes are not found in non-HIV-infected persons nor in
       HIV-infected chimpanzees. HIV-infected chimpanzees don't develop AIDS or
       suffer CD4 depletion. This association with disease and their observed
       specificity for uninfected CD4s suggest that these CTL may contribute to
       CD4-depletion in human HIV infection. Therefore, effective therapy for
       HIV infection may need to address the activity of these CTL. We have
       shown that these CTL can be specifically inhibited by incubation,
       immediately before cytotoxicity assays, with small amounts of a purified
       monoclonal antibody (mAb) 1F7. Equivalent amounts of isotype control
       mAbs had no effect. Longer incubation of CD8s from HIV-infected
       individuals with 1F7 caused apoptosis and reduced CTL-mediated
       cytotoxicity. 1F7 did not block killing mediated by allospecific CTL
       from either HIV-infected or non-HIV-infected individuals and also had no
       effect on natural killer (NK) cell-mediated killing of K562 cells.
       Therefore, 1F7 specifically inhibits cytotoxicity mediated by a distinct
       subset of CD8+ CTL selectively expanded in HIV infection. This subset
       includes CTL that kill uninfected CD4+ lymphocytes and might thereby
       contribute to CD4-depletion and disease progression. Agents such as 1F7
       that selectively target CD8s contributing to disease progression may
       have a role in effective therapy of HIV infection.
 DE    Antibodies, Monoclonal/IMMUNOLOGY/*PHARMACOLOGY  Antigens,
       CD4/*IMMUNOLOGY  Cytotoxicity, Immunologic/DRUG EFFECTS  Human  HIV
       Infections/*IMMUNOLOGY  Solubility  T-Lymphocytes, Cytotoxic/DRUG
       EFFECTS/*IMMUNOLOGY  T4 Lymphocytes/*IMMUNOLOGY  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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