Iyengar S, Finny JG, Schwartz DH; International Conference on AIDS.

Int Conf AIDS. 2002 Jul 7-12; 14: abstract no. MoPeA3080.

Dept. of Molec. Microbiol. &Immunol., Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States

BACKGROUND: Potent resistance to exogenous HIV in PBMCs of aviremic HIV+ donors may involve mechanisms not operative in partially resistant PBMCs of exposed uninfected (EU) donors or recipients of experimental HIV Vaccines. To elucidate naturally acquired vs. vaccine induced immunity, we examined mechanism and kinetics of viral suppression in aviremic individuals' PBMCs, capable of resisting infection with 100 TCID50 exogenous X4 or R5 HIV. METHODS: R5 or X4 HIV carrying Tat regulated huGFP in place of nef were added at 100 ng p24/ml to whole, or CD8 depleted, PBMCs that had been stimulated for 3 days with anti-CD3 + IL-2. Infected cells expressing HIV & GFP genes were scored by flow cytometry. RESULTS: In normal PBMCs, X4 or R5 HIV GFP expression was detected 18 h post-infection, the earliest time tested, increasing over the next 7 days. PBMCs from aviremic HIV+ donors were GFP(-) for X4 and R5 virus at 18 h of exposure, remaining negative for 7 days. Following immunodepletion of CD8+ cells from resistant PBMCs, remaining cells supported exogenous HIV infection with the same kinetics as non-resistant PBMCs, with GFP detected at 18 hrs, increasing over 7 days. CONCLUSION: GFP detection 18 h after addition of HIV permits study of first round infection kinetics. Early blockade could be at entry, integration, or post-integration, but for CD8+ cell responses, it suggests CTL or cytokine secreting cells in a highly activated state (without days of pCTL stimulation), or antibody-dependent cell mediated cytotoxicity (ADCC) by pre-armed CD8+ cells. Given undetectable viral replication in our aviremic donors, high levels of pre-activated, anti-HIV CD8 cells would be surprising. It is even more doubtful that vaccines will induce persistently activated CTL. GFP kinetics in moderately resistant PBMCs of EU and HIV vaccinees may reveal delayed suppression, suggesting pCTL restimulation. Early GFP suppression will suggest ADCC.

Publication Types:

• Meeting Abstracts

Keywords:

• Acquired Immunodeficiency Syndrome
• CD8-Positive T-Lymphocytes
• Genes, tat
• HIV Infections
• HIV Seropositivity
• T-Lymphocytes, Cytotoxic
• genetics

Other ID:

• GWAIDS0015976

UI: 102253474

From Meeting Abstracts