The infiltration kinetics of simian immunodeficiency virus-specific T cells drawn to sites of high antigenic stimulation determines local in vivo viral escape

^*Unité de Rétrovirologie Moléculaire and ^†Unité de Physiopathologie des Infections Lentivirales, Institut Pasteur, 28, Rue du Dr. Roux, 75724 Paris Cedex 15, France

Edited by Anthony S. Fauci, National Institutes of Health, Bethesda, MD, and approved September 7, 2001 (received for review July 9, 2001)

Abstract

Despite vigorous cell-mediated immune responses to human and simian immunodeficiency viruses (HIV/SIV) the immune system is unable to clear latently infected resting T cells. These infected cells are reactivated by antigenic stimulation, leading to viral replication. By using the SIV/macaque model of HIV pathogenesis, the dynamics of T cell infiltration into delayed type hypersensitivity sites specific for the purified protein derivative of bacillus Calmette–Guérin have been studied. Early viral mRNA synthesis coincided with the infiltration of antigen-specific T cells. When the infiltration of anti-SIV-specific T cells was rapid compared with the kinetics of viral assembly, the sites were sterilized before the transition to late viral mRNA synthesis occurred. When their infiltration was slow, ephemeral foci of replication were identified. These findings were paralleled by plasma viremia; low viremia coincided with rapid sterilization of the delayed type hypersensitivity sites, whereas high load was found in association with local replication and delayed sterilization. These data suggest that although effective local control of SIV is possible once antiviral T lymphocytes have arrived on site, the slower deployment of these T cells may allow the virus to escape and thus to reseed the pool of memory T cells.

Footnotes

↵ ‡ To whom reprint requests should be addressed. E-mail: simon{at}pasteur.fr.
↵ § Present address: Laboratoire d'Immunologie, Hopital de l'Hotel Dieu, 3850 rue Saint Urbain, Montreal, QC, Canada H2W 1T8.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

SIV,

simian immunodeficiency virus;

CTL,

cytotoxic T lymphocyte;

DTH,

delayed type hypersensitivity;

BCG,

bacillus Calmette–Guérin;

PPD,

purified protein derivative;

PBMC,

peripheral blood mononuclear cell;

ISH,

in situ hybridization;

RT-PCR,

reverse transcription–PCR;

TCR,

T cell antigen receptor