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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Impact of HIV on CD8+ T cell CD57 expression is distinct from that of CMV and aging
PLoS ONE, Volume 9, No. 2, Article e89444, Year 2014
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Description
Background: Chronic antigenic stimulation by cytomegalovirus (CMV) is thought to increase "immunosenesence" of aging, characterized by accumulation of terminally differentiated CD28- CD8 + T cells and increased CD57, a marker of proliferative history. Whether chronic HIV infection causes similar effects is currently unclear. Methods: We compared markers of CD8+ T cell differentiation (e.g., CD28, CD27, CCR7, CD45RA) and CD57 expression on CD28- CD8+ T cells in healthy HIV-uninfected adults with and without CMV infection and in both untreated and antiretroviral therapy (ART)-suppressed HIV-infected adults with asymptomatic CMV infection. Results: Compared to HIV-uninfected adults without CMV (n = 12), those with asymptomatic CMV infection (n = 31) had a higher proportion of CD28-CD8+ T cells expressing CD57 (P = 0.005). Older age was also associated with greater proportions of CD28-CD8+ T cells expressing CD57 (rho: 0.47, P = 0.007). In contrast, untreated HIV-infected CMV+ participants (n = 55) had much lower proportions of CD28- CD8+ cells expressing CD57 than HIV-uninfected CMV+ participants (P<0.0001) and were enriched for less well-differentiated CD28- transitional memory (T TR) CD8+ T cells (P<0.0001). Chronically HIV-infected adults maintaining ART-mediated viral suppression (n = 96) had higher proportions of CD28-CD8 + T cells expressing CD57 than untreated patients (P<0.0001), but continued to have significantly lower levels than HIV-uninfected controls (P = 0.001). Among 45 HIV-infected individuals initiating their first ART regimen, the proportion of CD28-CD8+ T cells expressing CD57 declined (P<0.0001), which correlated with a decline in percent of transitional memory CD8+ T cells, and appeared to be largely explained by a decline in CD28-CD57- CD8+ T cell counts rather than an expansion of CD28-CD57+ CD8+ T cell counts. Conclusions: Unlike CMV and aging, which are associated with terminal differentiation and proliferation of effector memory CD8+ T cells, HIV inhibits this process, expanding less well-differentiated CD28- CD8+ T cells and decreasing the proportion of CD28- CD8+ T cells that express CD57. © 2014 Lee et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3937334/bin/pone.0089444.s001.tiff
https://efashare.b-cdn.net/share/pmc/articles/PMC3937334/bin/pone.0089444.s002.tiff
https://efashare.b-cdn.net/share/pmc/articles/PMC3937334/bin/pone.0089444.s003.tiff
Authors & Co-Authors
Lee, Sulggi A.
United States, San Francisco
University of California, San Francisco
Sinclair, Elizabeth
United States, San Francisco
University of California, San Francisco
Hatano, Hiroyu
United States, San Francisco
University of California, San Francisco
Hsue, Priscilla Ying
United States, San Francisco
University of California, San Francisco
Epling, Lorrie
United States, San Francisco
University of California, San Francisco
Hecht, Frederick M.
United States, San Francisco
University of California, San Francisco
Bangsberg, David R.
United States, Boston
Massachusetts General Hospital
Uganda, Mbarara
Mbarara University of Science and Technology
Martin, Jeffrey N.
United States, San Francisco
University of California, San Francisco
McCune, Joseph M.
United States, San Francisco
University of California, San Francisco
Deeks, Steven G.
United States, San Francisco
University of California, San Francisco
Hunt, Peter W.
United States, San Francisco
University of California, San Francisco
Statistics
Citations: 87
Authors: 11
Affiliations: 3
Identifiers
Doi:
10.1371/journal.pone.0089444
e-ISSN:
19326203
Research Areas
Infectious Diseases