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Death of CD4+ T cells from lymph nodes during primary SIVmac251 infection predicts the rate of AIDS progression.

Authors :
Viollet L
Monceaux V
Petit F
Ho Tsong Fang R
Cumont MC
Hurtrel B
Estaquier J
Source :
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2006 Nov 15; Vol. 177 (10), pp. 6685-94.
Publication Year :
2006

Abstract

Immunological and virological events that occur during the earliest stages of SIV infection are now considered to have a major impact on subsequent disease progression. In the present study, we demonstrate a clear correlation between progression to AIDS and the rate of in vitro CD4+ (but not CD8+) T cell death in lymph nodes. The dying CD4+ T cells were effector memory T cells, which are critical for the immune response to pathogens. However, there was no correlation between the rate of the viral replication within lymph nodes and the extent of Fas ligand-mediated death, despite the increased sensitivity of CD4+ T cells to death in response to recombinant human Fas ligand. CD4+ T cell death was caspase and apoptosis-inducing factor independent but was clearly associated with mitochondrion damage. Interestingly, higher expression levels of the active form of Bak, a proapoptotic molecule involved in mitochondrial membrane permeabilization, were observed in SIV-infected macaques progressing more rapidly to AIDS. Finally, we demonstrated that the strain of SIV we used requires CCR5 and BOB/GRP15 molecules as coreceptors and caused death of unstimulated noncycling primary CD4+ T cells. Altogether, these results demonstrate that CD4+ T cell death occurring early after SIV infection is a crucial determinant of progression to AIDS and that it is mediated by the intrinsic death pathway.

Details

Language :
English
ISSN :
0022-1767
Volume :
177
Issue :
10
Database :
MEDLINE
Journal :
Journal of immunology (Baltimore, Md. : 1950)
Publication Type :
Academic Journal
Accession number :
17082581
Full Text :
https://doi.org/10.4049/jimmunol.177.10.6685