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1994-10-25
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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
protected by Copyright Law (Title 17, U.S.Code).