The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
CD4 T Cell Depletion Is Linked Directly to Immune Activation in the Pathogenesis of HIV-1 and HIV-2 but Only Indirectly to the Viral Load
Open accessAbstract
The causal relationships among CD4 cell depletion, HIV replication, and immune activation are not well understood. HIV-2 infection, “nature’s experiment” with inherently attenuated HIV disease, provides additional insights into this issue. We report the finding that in HIV-2 and HIV-1 patients with a comparable degree of CD4 depletion the imbalance in the relative sizes of the naive and memory T cell populations and the up-regulation of CD4 and CD8 cell activation markers (HLA-DR, CD38, CD69, Fas molecules) are similar, even though the viral load in the plasma of HIV-2-infected patients is two orders of magnitude lower than in HIV-1 patients and HIV-2 patients are known to have slower rates of CD4 T cell decline and a better clinical prognosis. Moreover, we found a similar increase in the frequency of cycling CD4 T cells (Ki67+), which was in strong correlation with the expression of activation markers. Finally, the level of T cell anergy, as assessed by the proliferative responses to CD3 stimulation and to a panel of microbial Ags, proved to be comparable in HIV-1 and HIV-2 patients with a similar degree of CD4 depletion despite large differences in viral load. Our data are consistent with a direct causal relationship between immune activation and CD4 cell depletion in HIV disease and an only indirect relation of these parameters to the virus replication rate. Invoking the concept of proximal immune activation and virus transmission, which links efficient transmission of virus to local cell activation and proliferation in response to Ags and inflammation, we propose an integrative interpretation of the data and suggest that strongly elevated immune activation induces CD4 cell depletion and not vice versa, with potential implications for the choice of treatment strategies.
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Cites
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Cited by
Deeks, S. G., Kitchen, C. M. R., Liu, L., Guo, H., Gascon, R., Narváez, A. B., Hunt, P., Martin, J. N., Kahn, J. O., Levy, J., et al. (2004) · Blood · doi:10.1182/blood-2003-09-3333 · Cited by 804
Moore, J. P., Kitchen, S. G., Pugach, P., & Zack, J. A. (2004) · AIDS Research and Human Retroviruses · doi:10.1089/088922204322749567 · Cited by 494
Jacquelin, B., Mayau, V., Targat, B., Liovat, A.-S., Kunkel, D., Petitjean, G., Dillies, M.-A., Roques, P., Butor, C., Silvestri, G., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci40093 · Cited by 481
Immune Activation and CD8+ T-Cell Differentiation towards Senescence in HIV-1 Infection
Papagno, L., Spina, C. A., Marchant, A., Salio, M., Rufer, N., Little, S., Dong, T., Chesney, G., Waters, A., Easterbrook, P., et al. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020020 · Cited by 478
HIV‐associated chronic immune activation
Paiardini, M., & Müller‐Trutwin, M. (2013) · Immunological Reviews · doi:10.1111/imr.12079 · Cited by 451
Metadata
- Authors
- Sousa, A. E., Carneiro, J., Meier-Schellersheim, M., Grossman, Z., & Victorino, R. M. M.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-09
- Volume
- 169
- Issue
- 6
- Pages
- 3400-3406
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2128620327
- Cited by
- 507
- References
- 39
- FWCI
- 7.81
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: CD4 T Cell Depletion Is Linked Directly to Immune Activation in the Pathogenesis of HIV-1 and HIV-2 but Only Indirectly to the Viral Load. https://app.cochat.ai/papers/10.4049/jimmunol.169.6.3400
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- Sousa, A. E., Carneiro, J., Meier-Schellersheim, M., Grossman, Z., & Victorino, R. M. M. (2002). CD4 T Cell Depletion Is Linked Directly to Immune Activation in the Pathogenesis of HIV-1 and HIV-2 but Only Indirectly to the Viral Load. The Journal of Immunology. https://doi.org/10.4049/jimmunol.169.6.3400
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
