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).