dc.contributor.author | Juno, Jennifer A | |
dc.contributor.author | Stalker, Andrew T | |
dc.contributor.author | Waruk, Jillian LM | |
dc.contributor.author | Oyugi, Julius | |
dc.contributor.author | Kimani, Makobu | |
dc.contributor.author | Plummer, Francis A | |
dc.contributor.author | Kimani, Joshua | |
dc.contributor.author | Fowke, Keith R | |
dc.date.accessioned | 2015-04-08T13:13:27Z | |
dc.date.available | 2015-04-08T13:13:27Z | |
dc.date.issued | 2015 | |
dc.identifier.citation | Retrovirology. 2015; 12: 17. | en_US |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332911/pdf/12977_2015_Article_142.pdf | |
dc.identifier.uri | http://hdl.handle.net/11295/81954 | |
dc.description.abstract | Background:
LAG-3 is a potent negative regulator of the immune response but its impact in HIV infection in
poorly understood. Unlike exhaustion markers such as PD-1, Tim-3, 2B4 and CD160, LAG-3 is poorly expressed on
bulk and antigen-specific T cells during chronic HIV infection and its expression on innate lymphocyte subsets is
not well understood. The aim of this study was to assess LAG-3 expression and association with cellular dysfunction
on T cells, NK cells and iNKT cells among a cohort of healthy and HIV-infected female sex workers in Nairobi, Kenya.
Results:
Ex vivo LAG-3 expression was measured by multiparametric flow cytometry, and plasma cytokine/chemokine
concentrations measured by bead array. Although LAG-3 expression on bulk T cells was significantly increased among
HIV-infected women, the proportion of cells expressing the marker was extremely low. In contrast, LAG-3 was more
highly expressed on NK and iNKT cells and was not reduced among women treated with ART. To assess the functional
impact of LAG-3 on iNKT cells, iNKT cytokine production was measured in response to lipid (
α
GalCer) and PMA/Io
stimulation by both flow cytometry and cytokine bead array. iNKT cytokine production is profoundly altered by
both HIV infection and treatment, and LAG-3, but not PD-1, expression is associated with a reduction in iNKT IFN
γ
production.
Conclusions:
LAG-3 does not appear to mediate T cell exhaustion in this African population, but is instead
expressed on innate lymphocyte subsets including iNKT cells. HIV infection alters iNKT cytokine production patterns
and LAG-3 expression is uniquely associated with iNKT dysfunction. The continued expression of LAG-3 during
treatment suggests it may contribute to the lack of innate immune reconstitution commonly observed during ART | en_US |
dc.language.iso | en | en_US |
dc.publisher | University of Nairobi | en_US |
dc.subject | Exhaustion, iNKT cells, LAG-3 protein human, HIV, CD223, Immune dysfunction | en_US |
dc.title | Elevated expression of LAG-3, but not PD-1, is associated with impaired iNKT cytokine production during chronic HIV-1 infection and treatment | en_US |
dc.type | Article | en_US |
dc.type.material | en_US | en_US |