Lee S.A., Sinclair E., Hatano H., Hsue P.Y., Epling L., Hecht F.M., Bangsberg D.R., Martin J.N., McCune J.M., Deeks S.G., Hunt P.W.
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
Lee, S.A., Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, United States; Sinclair, E., Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, United States; Hatano, H., Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, United States; Hsue, P.Y., Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, United States; Epling, L., Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, United States; Hecht, F.M., Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, United States; Bangsberg, D.R., 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; Martin, J.N., Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, United States; McCune, J.M., Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, United States; Deeks, S.G., Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, United States; Hunt, P.W., Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, United States
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.
#2008047, Doris Duke Charitable Foundation; K24AI069994, NIAID, Doris Duke Charitable Foundation; P01AI076174, NIAID, Doris Duke Charitable Foundation; R21 AI087035, NIAID, Doris Duke Charitable Foundation; R21AI078774, NIAID, Doris Duke Charitable Founda