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

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

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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.

Original languageEnglish (US)
Article numbere18779
JournalPloS one
Issue number4
StatePublished - 2011
Externally publishedYes

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Innate and adaptive immune responses both contribute to pathological cd4 t cell activation in hiv-1 infected ugandans'. Together they form a unique fingerprint.

Cite this