Elevated expression of LAG-3, but not PD-1, is associated with impaired iNKT cytokine production during chronic HIV-1 infection and treatment
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Date
2015Author
Juno, Jennifer A
Stalker, Andrew T
Waruk, Jillian LM
Oyugi, Julius
Kimani, Makobu
Plummer, Francis A
Kimani, Joshua
Fowke, Keith R
Language
enMetadata
Show full item recordAbstract
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
URI
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332911/pdf/12977_2015_Article_142.pdfhttp://hdl.handle.net/11295/81954
Citation
Retrovirology. 2015; 12: 17.Publisher
University of Nairobi
Collections
- Faculty of Health Sciences (FHS) [10385]