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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.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2002 Sep 15; Vol. 169 (6), pp. 3400-6. - Publication Year :
- 2002
-
Abstract
- 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.
- Subjects :
- Biomarkers blood
CD3 Complex pharmacology
CD4-CD8 Ratio
CD4-Positive T-Lymphocytes metabolism
CD4-Positive T-Lymphocytes virology
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes metabolism
Cell Cycle immunology
Cells, Cultured
HIV Infections pathology
HIV Infections virology
Humans
Immunologic Memory
Immunophenotyping
Interphase immunology
Lymphopenia pathology
Lymphopenia virology
Mitogens pharmacology
Up-Regulation immunology
fas Receptor biosynthesis
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes pathology
HIV Infections immunology
HIV-1 immunology
HIV-2 immunology
Lymphocyte Activation
Lymphopenia immunology
Viral Load
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 169
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 12218162
- Full Text :
- https://doi.org/10.4049/jimmunol.169.6.3400