CD8+ T-lymphocyte activation in HIV-1 disease reflects an aspect of pathogenesis distinct from viral burden and immunodeficiency.
The CD8+ T-cell response is central to control and eventual elimination of persistent viral infections. Although it might be expected that CD8+ T-cell activation would be associated with a better clinical outcome during viral infections, in long-term HIV-1 infection, high levels of CD8+ T-cell activation are instead associated with faster disease progression. In this study, cell surface expression of CD38, a flow cytometric marker of T-cell activation of CD8+ T cells, had predictive value for HIV-1 disease progression that was in part independent of the predictive value of plasma viral burden and CD4+ T-cell number. Measurements of CD38 antigen expression on CD8+ T cells in HIV-1-infected patients may be of value for assessing prognosis and the impact of therapeutic interventions. The pathogenetic reason why CD8+ T-cell activation is associated with poor outcome in HIV-1 disease remains unknown. Possibly CD8+ T-cell activation contributes to immunologic exhaustion, hyporesponsiveness of T cells to their cognate antigens, or perturbations in the T-cell receptor repertoire.
Liu
Z
Z
Department of Epidemiology, University of California-Los Angeles School of Public Health, 90095-1745, USA.
Cumberland
W G
WG
Hultin
L E
LE
Kaplan
A H
AH
Detels
R
R
Giorgi
J V
JV
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016009:Chi-Square Distribution; D015331:Cohort Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000032:analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000998:Antiviral Agents; D015415:Biomarkers; D008562:Membrane Glycoproteins; D012367:RNA, Viral; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1