Antigen-driven C-C Chemokine-mediated HIV-1 Suppression by CD4+ T Cells from Exposed Uninfected Individuals Expressing the Wild-type CCR-5 Allele

doi:10.1084/jem.186.3.455

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© The Rockefeller University Press, 0022-1007/1997/8/455/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 3, August 4, 1997 455-460

Brief Definitive Reports

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^*, and Alberto Beretta

From the ^* Department of Biological and Technological Research, San Raffaele Scientific Institute, Milan, Italy; and Centre Intégré de Recherches Biocliniques sur le SIDA (CIRBS), Paris, France

Despite repeated exposure to HIV-1, certain individuals remainpersistently uninfected. Such exposed uninfected (EU) peopleshow evidence of HIV-1–specific T cell immunity and, in rare cases, selective resistance to infection by macrophage-tropicstrains of HIV-1. The latter has been associated with a 32–basepair 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 responsesin 12 EU individuals who were either homozygous for the wild-typeCCR-5 allele or heterozygous for the deletion allele (CCR-5 ${Delta}$ 32).We have found evidence of an oligoclonal T cell response mediatedby helper T cells specific for a conserved region of the HIV-1envelope. These cells produce very high levels of C–Cchemokines when stimulated by the specific antigen and suppressselectively the replication of macrophage-tropic, but not Tcell–tropic, strains of HIV-1. These chemokine-producinghelper cells may be part of a protective immune response thatcould be potentially exploited for vaccine development.

Address correspondence to Dr. Alberto Beretta, Centre Intégréde Recherches Biocliniques sur le SIDA, 185 rue Raymond Losserand,75014 Paris, France. Phone: 33-1-44-12-31-74; FAX: 33-1-44-12-32-70; E-mail: cirbs{at}imaginet.fr

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