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Published online 20 November 2006 doi:10.1084/jem.20060134
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 12, 2661-2672
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ARTICLE

Induction of a virus-specific effector–memory CD4+ T cell response by attenuated SIV infection

Marie-Claire Gauduin1, Yi Yu1, Amy Barabasz1, Angela Carville3, Mike Piatak4, Jeffrey D. Lifson4, Ronald C. Desrosiers2, and R. Paul Johnson1,5

1 Division of Immunology, Division of 2 Microbiology, and Division of 3 Primate Medicine, New England Primate Research Center, Harvard Medical School, Southborough, MA 01772
4 AIDS Vaccine Program, Science Applications International Corporation Frederick, Inc., National Cancer Institute (NCI)-Frederick, Frederick, MD 21702
5 Partners AIDS Research Center, Infectious Disease Unit, Massachusetts General Hospital, Boston, MA 02115

CORRESPONDENCE Marie-Claire Gauduin: mcgauduin{at}sfbr.org

We investigated simian immunodeficiency virus (SIV)-specific CD4+ T cell responses in rhesus macaques chronically infected with attenuated or pathogenic SIV strains. Analysis of SIV{Delta}nef-infected animals revealed a relatively high frequency of SIV-specific CD4+ T cells representing 4–10% of all CD4+ T lymphocytes directed against multiple SIV proteins. Gag-specific CD4+ T cells in wild-type SIV-infected animals were 5–10-fold lower in frequency and inversely correlated with the level of plasma viremia. SIV-specific CD4+ cells from SIV{Delta}nef animals were predominantly CD27CD28CD45RAlowCCR7CCR5, consistent with an effector–memory subset, and included a fully differentiated CD45RA+CCR7 subpopulation. In contrast, SIV-specific CD4+ T cells from SIV-infected animals were mostly CD27+CD28+CD45RACCR7+CCR5+, consistent with an early central memory phenotype. The CD45RA+CCR7CD4+ subset from SIV{Delta}nef animals was highly enriched for effector CD4+ T cells, as indicated by the perforin expression and up-regulation of the lysosomal membrane protein CD107a after SIV Gag stimulation. SIV-specific CD4+ T cells in attenuated SIV-infected animals were increased in frequency in bronchioalveolar lavage and decreased in lymph nodes, consistent with an effector–memory T cell population. The ability of SIV{Delta}nef to induce a high frequency virus-specific CD4+ T cell response with direct effector function may play a key role in protective immunity produced by vaccination with attenuated SIV strains.


Abbreviations used: BAL, bronchoalveolar lavage; ICS, intracellular cytokine staining; SEA, staphylococcal enterotoxin A; SEB, staphylococcal enterotoxin B; SIV, simian immunodeficiency virus.

M.-C. Gauduin's present address is Dept. of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78245.


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