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1994-10-25
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Document 3247
DOCN M94A3247
TI Glucocorticoids rescue CD4+ T cells from activation-induced apoptosis
triggered by HIV-1.
DT 9412
AU Lu W; Salerno-Goncalvez R; Yuan J; Andrieu JM; Laboratory of Tumor
Immunology, Hopital Laennec, Universite de; Paris V, France.
SO Int Conf AIDS. 1994 Aug 7-12;10(1):12 (abstract no. 021A). Unique
Identifier : AIDSLINE ICA10/94369328
AB OBJECTIVE: Having observed an increase of the CD4 count in HIV+ patients
treated by prednisolone (Abstr., Andrieu Jean-Marie, et al), we
investigated the in vitro effects of glucocorticoids (GCC) on HIV+
T-cell apoptosis. METHODS: PBMC from HIV neg. donors were separated by
Ficoll-Hypaque gradient and CD4 and CD8 cells were purified by positive
selection. CD4, CD8 cells, and PBMC were incubated for 2 hrs with HIV-1
(primary isolates) at a MOI of 2 x 10(-4). Then, cells were cultured for
7 days with medium alone or anti-CD3 mAb (0.5 microgram/ml) with or
without hydrocortisone or prednisolone (0.1-1000 micrograms/ml). HIV
neg. cells served as control. Viral infection kinetics was assessed by
PCR and viral replication by RT-PCR and P24 ELISA. Cell survival (%
viable cell change from base line) was monitored every day by trypan
blue dye exclusion. Cell activation was evaluated by blast cell
transformation and interleukin 2 (IL2) receptor (CD25) expression (flow
cytometry), cell proliferation by [3H]-thymidine uptake, % apoptotic
cells by flow cytometric PI staining method, and % fragmented DNA by
fractioned DNA spectrophotometer. These tests were performed at 3-4 days
and 6-7 days. RESULTS: In HIV neg. CD4, CD8 cells, and PBMC, TCR/CD3
ligation induced proliferation (5-20 x 10(3) cpm) and weak apoptosis (<
10%), which resulted in an upregulation of cell survival (100-300%). In
HIV+ cells, proliferation declined in PBMC (5-10 x 10(3) cpm) and was
suppressed in CD4 cells (500-1000 cpm) while apoptosis increased
(20-50%) in both, resulting in a decreased cell survival (50% for PBMC
and -90% for CD4 cells) by day 7. In contrast, proliferation, apoptosis,
and cell survival of CD8 cells remained unchanged after exposure to
HIV-1. Under 1-10 micrograms/ml of GCC, apoptosis of HIV+ PBMC and CD4
cells was inhibited (5-15%) without modification of proliferation, while
cell survival was maintained in CD4 cells (5-10%) and % CD4 in PBMC
remained normal (> or = 30%). Under 100-1000 micrograms/ml of GCC, both
cell proliferation and apoptosis were inhibited while cell survival was
maintained. GCC failed to block IL-2-dependent blast transformation and
showed a > or = 50% reduction in the peak of viral production without
modification of the kinetics of viral replication. DISCUSSION AND
CONCLUSIONS: HIV-1 accelerates apoptotic cell death in PBMC and
fractionated CD4+ T cells upon to TCR/CD3 ligation. Pharmacological
doses of GCC antagonize the apoptotic pathway without significant
alteration of cell activation signaling.
DE Antigens, CD8 Apoptosis/*DRUG EFFECTS Cell Survival Cells, Cultured
Enzyme-Linked Immunosorbent Assay Human Hydrocortisone/*PHARMACOLOGY
*HIV-1 In Vitro Polymerase Chain Reaction Prednisolone/*PHARMACOLOGY
T-Lymphocyte Subsets/DRUG EFFECTS/MICROBIOLOGY/*PHYSIOLOGY T4
Lymphocytes/DRUG EFFECTS/MICROBIOLOGY/*PHYSIOLOGY Virus Replication
MEETING ABSTRACT
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).