Publication:
Innate and adaptive immune responses both contribute to pathological cd4 t cell activation in hiv-1 infected ugandans

Issued Date

2011-05-02

Resource Type

Article

ISSN

19326203

DOI

10.1371/journal.pone.0018779

Other identifier(s)

2-s2.0-79955384228

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

PLoS ONE. Vol.6, No.4 (2011)

Suggested Citation

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 Innate and adaptive immune responses both contribute to pathological cd4 t cell activation in hiv-1 infected ugandans. PLoS ONE. Vol.6, No.4 (2011). doi:10.1371/journal.pone.0018779 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/11321

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Title

Innate and adaptive immune responses both contribute to pathological cd4 t cell activation in hiv-1 infected ugandans

Author(s)

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

Other Contributor(s)

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

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.

Keyword(s)

Agricultural and Biological Sciences
 Biochemistry, Genetics and Molecular Biology

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/11321

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