title: Differential upregulation of CD38 on different T-cell subsets may influence the ability to reconstitute CD4+ T cells under successful highly active antiretroviral therapy.
abstract: BACKGROUND
  Immune activation is an independent surrogate marker of CD4 T-cell depletion in HIV-infected patients. Highly active antiretroviral therapy (HAART) reduces disease progression as a direct consequence of suppressing HIV replication. Immune function does not normalize completely in most subjects on HAART, however, perhaps reflecting residual HIV replication. So far, it is unclear to what extent immune activation may influence the evolution of CD4 T-cell counts in patients on HAART.
  
  
  METHODS
  The expression of CD38 on naive and memory subsets of CD4+ and CD8+ T cells was measured quantitatively by flow cytometry in 62 drug-naive HIV-positive and 30 HIV-uninfected controls. In addition, the evolution of this marker as well as that of some virologic parameters (plasma viremia and proviral load) and CD4 counts were assessed in 25 HIV-infected individuals who initiated HAART and were followed for 12 months.
  
  
  RESULTS
  The mean level of CD38 on memory CD4+ and CD8+ T cells as well as in naive CD8+ cells was significantly higher in drug-naive HIV-positive subjects than in HIV-negative controls. Moreover, it was highly correlated with viral load titers. In patients on successful HAART, immune activation declined in all T-cell subsets, particularly among memory CD8+ cells. It remained elevated with respect to HIV-negative controls, however, even after 12 months of HAART. There was a significant correlation between the CD8+ T-cell activation decay and the increase of CD4+ T cells on HAART. Patients with the highest decline in CD8 activation were those showing the highest CD4 T-cell gains after 12 months of therapy.
  
  
  CONCLUSIONS
  The level of CD38 expression on different T-cell subsets is differentially upregulated in drug-naive HIV-infected patients. After successful HAART, immune activation decreases in all T-cell subsets, although it still remains elevated in most cases after 12 months of HAART. The extent of immune deactivation under successful HAART correlates with the ability to reconstitute CD4 counts.
authors.affiliation: Service of Infectious Diseases, Hospital Carlos III, Madrid, Spain. jbenito1@hotmail.com
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Benito
authors.forename: Mariola
authors.initials: M
authors.lastname: López
authors.forename: Sara
authors.initials: S
authors.lastname: Lozano
authors.forename: Celia
authors.initials: C
authors.lastname: Ballesteros
authors.forename: Pilar
authors.initials: P
authors.lastname: Martinez
authors.forename: Juan
authors.initials: J
authors.lastname: González-Lahoz
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000235:genetics*; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008137:Longitudinal Studies; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008297:Male; D008562:Membrane Glycoproteins; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013997:Time Factors; D015854:Up-Regulation; D019562:Viral Load
chemical_list: D015703:Antigens, CD; D008562:Membrane Glycoproteins; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1