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
Ana E. Sousa,Jorge Carneiro,Martin Meier-Schellersheim,Zvi Grossman,Zvi Grossman,Rui M. M. Victorino +5 more
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TLDR
The 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.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.read more
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HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation
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TL;DR: The results suggest that viral eradication might be achieved through the combined use of strategic interventions targeting viral replication and drugs that interfere with the self renewal and persistence of proliferating memory T cells.
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Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load.
Steven G. Deeks,Christina M. R. Kitchen,Lea Liu,Hua Guo,Ron Gascon,Amy Narvaez,Peter W. Hunt,Jeffrey N. Martin,James O. Kahn,Jay A. Levy,Michael S. McGrath,Frederick Hecht +11 more
TL;DR: Data indicate that immunologic activation set point is established early in HIV infection, and that this set point determines the rate at which CD4+ T cells are lost over time.
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Immune activation and inflammation in HIV-1 infection: causes and consequences.
Victor Appay,Delphine Sauce +1 more
TL;DR: A simplified model of HIV pathogenesis is proposed, which links together the three major facets of HIV‐1 infection: the massive depletion of CD4+ T cells, the paradoxical immune activation and the exhaustion of regenerative capacity.
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Nonpathogenic SIV infection of sooty mangabeys is characterized by limited bystander immunopathology despite chronic high-level viremia.
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TL;DR: It is reported here that SIV-infected mangabeys maintain preserved T lymphocyte populations and regenerative capacity and manifest far lower levels of aberrant immune activation and apoptosis than are seen in pathogenic SIV and HIV infections.
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Relationship between T Cell Activation and CD4+ T Cell Count in HIV-Seropositive Individuals with Undetectable Plasma HIV RNA Levels in the Absence of Therapy
Peter W. Hunt,Jason M. Brenchley,Elizabeth Sinclair,Joseph M. McCune,Michelle E. Roland,Kimberly Page-Shafer,Priscilla Y. Hsue,Brinda Emu,Melissa R. Krone,Harry Lampiris,Daniel C. Douek,Jeffrey N. Martin,Steven G. Deeks +12 more
TL;DR: HIV controllers have abnormally high T cell activation levels, which may contribute to progressive CD4(+) T cell loss even without measurable viremia.
References
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