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

L Viollet, V Monceaux, F Petit, RHT Fang… - The Journal of …, 2006 - journals.aai.org
L Viollet, V Monceaux, F Petit, RHT Fang, MC Cumont, B Hurtrel, J Estaquier
The Journal of Immunology, 2006journals.aai.org
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 …
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.
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