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Title: Innate and adaptive immune responses both contribute to pathological cd4 t cell activation in hiv-1 infected ugandans
Authors: Michael A. Eller
Kim G. Blom
Veronica D. Gonzalez
Leigh Anne Eller
Prossy Naluyima
Oliver Laeyendecker
Thomas C. Quinn
Noah Kiwanuka
David Serwadda
Nelson K. Sewankambo
Boonrat Tasseneetrithep
Maria J. Wawer
Ronald H. Gray
Mary A. Marovich
Nelson L. Michael
Mark S. de Souza
Fred Wabwire-Mangen
Merlin L. Robb
Jeffrey R. Currier
Johan K. Sandberg
Makerere University
U.S. Military HIV Research Program
Karolinska University Hospital
National Institute of Allergy and Infectious Diseases
The Johns Hopkins School of Medicine
Uganda Virus Research Institut
Mahidol University
Columbia University Medical Center
Johns Hopkins University
Armed Forces Research Institute of Medical Sciences, Thailand
Keywords: Agricultural and Biological Sciences;Biochemistry, Genetics and Molecular Biology
Issue Date: 2-May-2011
Citation: PLoS ONE. Vol.6, No.4 (2011)
Abstract: HIV-1 disease progression is associated with persistent immune activation. However, the nature of this association is incompletely understood. Here, we investigated immune activation in the CD4 T cell compartment of chronically HIV-1 infected individuals from Rakai, Uganda. Levels of CD4 T cell activation, assessed as co-expression of PD-1, CD38 and HLA-DR, correlated directly to viral load and inversely to CD4 count. Deeper characterization of these cells indicated an effector memory phenotype with relatively frequent expression of Ki67 despite their PD-1 expression, and levels of these cells were inversely associated with FoxP3+ regulatory T cells. We therefore use the term deregulated effector memory (DEM) cells to describe them. CD4 T cells with a DEM phenotype could be generated by antigen stimulation of recall responses in vitro. Responses against HIV-1 and CMV antigens were enriched among the DEM CD4 T cells in patients, and the diverse Vβ repertoire of DEM CD4 T cells suggested they include diverse antigen-specificities. Furthermore, the levels of DEM CD4 T cells correlated directly to soluble CD14 (sCD14) and IL-6, markers of innate immune activation, in plasma. The size of the activated DEM CD4 T cell subset was predictive of the rate of disease progression, whereas IL-6 was only weakly predictive and sCD14 was not predictive. Taken together, these results are consistent with a model where systemic innate immune activation and chronic antigen stimulation of adaptive T cell responses both play important roles in driving pathological CD4 T cell immune activation in HIV-1 disease.
ISSN: 19326203
Appears in Collections:Scopus 2011-2015

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