title: Impact of HIV on CD8+ T cell CD57 expression is distinct from that of CMV and aging.
abstract: 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 (TTR) 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.
authors.affiliation: Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Sulggi A
authors.initials: SA
authors.lastname: Lee
authors.affiliation: Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sinclair
authors.affiliation: Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Hiroyu
authors.initials: H
authors.lastname: Hatano
authors.affiliation: Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Priscilla Y
authors.initials: PY
authors.lastname: Hsue
authors.affiliation: Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Lorrie
authors.initials: L
authors.lastname: Epling
authors.affiliation: Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hecht
authors.affiliation: Department of Medicine, Massachusetts General Hospital and Harvard School of Public Health, Harvard Medical School, Boston, Massachusetts, United States of America ; Department of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda.
authors.forename: David R
authors.initials: DR
authors.lastname: Bangsberg
authors.affiliation: Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.affiliation: Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: McCune
authors.affiliation: Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.affiliation: Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hunt
mesh_terms: D000328:Adult; D000375:Aging / Q000276:immunology*; D023241:Antiretroviral Therapy, Highly Active; D018106:CD28 Antigens / Q000378:metabolism; D018959:CD57 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D003430:Cross-Sectional Studies; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged
chemical_list: D018106:CD28 Antigens; D018959:CD57 Antigens