Papagno, L;
Spina, CA;
Marchant, A;
Salio, M;
Rufer, N;
Little, S;
Dong, T;
... Appay, V; + view all
(2004)
Immune activation and CD8(+) T-cell differentiation towards senescence in HIV-1 infection.
PLOS BIOL
, 2
(2)
, Article e20. 10.1371/journal.pbio.0020020.
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Abstract
Progress in the fight against the HIV/AIDS epidemic is hindered by our failure to elucidate the precise reasons for the onset of immunodeficiency in HIV-1 infection. Increasing evidence suggests that elevated immune activation is associated with poor outcome in HIV-1 pathogenesis. However, the basis of this association remains unclear. Through ex vivo analysis of virus-specific CD8(+) T-cells and the use of an in vitro model of naive CD8(+) T-cell priming, we show that the activation level and the differentiation state of T-cells are closely related. Acute HIV-1 infection induces massive activation of CD8(+) T-cells, affecting many cell populations, not only those specific for HIV-1, which results in further differentiation of these cells. HIV disease progression correlates with increased proportions of highly differentiated CD8+ T-cells, which exhibit characteristics of replicative senescence and probably indicate a decline in T-cell competence of the infected person. The differentiation of CD8(+) and CD4(+) T-cells towards a state of replicative senescence is a natural process. It can be driven by excessive levels of immune stimulation. This may be part of the mechanism through which HIV-1-mediated immune activation exhausts the capacity of the immune system.
| Type: | Article |
|---|---|
| Title: | Immune activation and CD8(+) T-cell differentiation towards senescence in HIV-1 infection |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pbio.0020020 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pbio.0020020 |
| Language: | English |
| Additional information: | © 2004 Papagno et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | IMMUNODEFICIENCY-VIRUS-INFECTION, REPLICATIVE SENESCENCE, CYTOMEGALOVIRUS SEROPOSITIVITY, LYMPHOCYTE SUBPOPULATIONS, DISEASE PROGRESSION, TELOMERE LENGTH, SOOTY MANGABEYS, ANTIGEN, MEMORY, RESPONSES |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/139551 |
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