title: Highly active antiretroviral therapy in patients infected with human immunodeficiency virus increases CD40 ligand expression and IL-12 production in cells ex vivo.
abstract: Highly active anti-retroviral therapy (HAART) restores CD4(+) T-cell numbers in the periphery; however, its efficacy in restoring functional immunity is not fully elucidated. Here we evaluated longitudinal changes in the expression of several key markers of T-cell activation, namely CD40 ligand (CD154), OX40 (CD134), or CD69, after anti-CD3/CD28 activation, as well as levels of IL-12 production after Staphylococcus aureus Cowan stimulation in 28 HIV-infected adult patients. Patients were followed up to 12 mo post-HAART initiation. Viral burdens and CD4 cell counts were measured at the same time points. A control group of 15 HIV-uninfected adult subjects was included for comparison. Significant increases in CD40L and OX40 expression, but not of CD69 expression, were observed over time in the overall patient population, and more particularly in patients with baseline CD4 counts lower than or equal to 200 cells/μL, or those with baseline viral loads lower than or equal to 10(5) RNA copies/mL. Similar increases were seen for IL-12 production. Viral loads were inversely associated with CD40L expression or IL-12 production in a mixed linear model analysis, while CD4 counts were directly associated. CD40L expression and IL-12 production were significantly correlated. In conclusion, HAART-mediated control of viral replication led to partial restoration of CD40L upregulation/expression, and to increased IL-12 production, but the magnitude of the response depended on the baseline characteristics of the treated patients.
authors.affiliation: Division of Molecular Immunology, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH 45229, USA.
authors.forename: Alice M
authors.initials: AM
authors.lastname: Nyakeriga
authors.forename: Jun
authors.initials: J
authors.lastname: Ying
authors.forename: Norah J
authors.initials: NJ
authors.lastname: Shire
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Fichtenbaum
authors.forename: Claire A
authors.initials: CA
authors.lastname: Chougnet
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D023201:CD40 Ligand / Q000096:biosynthesis*; D005260:Female; D006678:HIV / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D053278:OX40 Ligand / Q000096:biosynthesis; D013211:Staphylococcus aureus / Q000276:immunology; D019562:Viral Load; D014766:Viremia
chemical_list: D019380:Anti-HIV Agents; D053278:OX40 Ligand; C089251:TNFSF4 protein, human; D023201:CD40 Ligand; D018664:Interleukin-12