Impact of HIV on CD8+ T cell CD57 expression is distinct from that of CMV and aging
Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, United States; Department of Medicine, Massachusetts General Hospital, Harvard School of Public Health, Boston, MA, United States; Department of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda
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.
anti human immunodeficiency virus agent; CD27 antigen; CD28 antigen; CD45RA antigen; CD57 antigen; chemokine receptor CCR7; chemokine receptor CX3CR1; adult; aging; antigen expression; article; CD8+ T lymphocyte; cell count; cell differentiation; cell division; clinical article; controlled study; Cytomegalovirus; cytomegalovirus infection; effector cell; female; highly active antiretroviral therapy; human; Human immunodeficiency virus; Human immunodeficiency virus infection; innate immunity; male; memory cell; morbidity; mortality; Uganda; Adult; Aging; Antigens, CD28; Antigens, CD57; Antiretroviral Therapy, Highly Active; CD8-Positive T-Lymphocytes; Cross-Sectional Studies; Cytomegalovirus; Cytomegalovirus Infections; Female; HIV Infections; HIV-1; Humans; Immunophenotyping; Lymphocyte Count; Male; Middle Aged
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