Antigen-driven C-C chemokine-mediated HIV-1 suppression by CD4+ T cells from exposed uninfected individuals expressing the wild-type CCR-5 allele

Lucinda Furci, Gabriella Scarlatti, Samuele Burastero, Giuseppe Tambussi, Claudia Colognesi, Caroline Quillent, Renato Longhi, Patrizia Loverro, Barbara Borgonovo, Davide Gaffi, Emily Carrow, Mauro Malnati, Paolo Lusso, Antonio G. Siccardi, Adriano Lazzarin, Alberto Beretta

Research output: Contribution to journalArticlepeer-review

Abstract

Despite repeated exposure HIV-1, certain individuals remain persistently uninfected. Such exposed uninfected (EU) people show evidence of HIV-1- specific T cell immunity and, in rate cases, selective resistance to infection by macrophage-tropic strains of HIV-1. The latter has been associated with a 32-base pair deletion in the C-C chemokine receptor gene CCR-5, the major coreceptor of macrophage-tropic strains of HIV-1. We have undertaken an analysis of the HIV-specific T cell responses in 12 EU individuals who were either homozygous for the wild-type CCR-5 allele or heterozygous for the deletion allele (CCR-5Δ32). We have found evidence of an oligoclonal T cell response mediated by helper T cells specific for a conserved region of the HIV-1 envelope. These cells produce very high levels of C-C chemokines when stimulated by the specific antigen and suppress selectively the replication of macrophage-tropic, but not T cell-tropic, strains of HIV-1. These chemokine-producing helper cells may be part of a protective immune response that could be potentially exploited for vaccine development.

Original languageEnglish
Pages (from-to)455-460
Number of pages6
JournalJournal of Experimental Medicine
Volume186
Issue number3
DOIs
Publication statusPublished - Aug 4 1997

ASJC Scopus subject areas

  • Immunology

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