title: Increased CD154 expression in uninfected infants born to HIV-positive mothers exposed to antiretroviral prophylaxis.
abstract: Although prevention of mother-to-child HIV transmission by antiretroviral drugs has been shown to be effective, the short- and long-term effects of treatment are not well known. Several reports suggest that antiretroviral drugs act not only by inhibiting viral replication, but also by improving antiviral immunity. In particular, treatment with nucleoside analogs was found to increase CD40 ligand (CD40L; CD154) levels, an inducible molecule expressed on activated T lymphocytes. The present study investigated potential immunostimulatory effects of antiretroviral treatment (ART) in uninfected HIV-exposed infants, receiving either ante- or postnatal therapy to reduce the transmission rate. To this end, we analyzed CD40L expression in unstimulated lymphocytes from peripheral blood samples of uninfected infants vertically exposed to HIV and subjected to ART. The CD45 PanLeucogating strategy was applied in flow cytometry to analyze the lymphocytes of 41 cases and 64 age-matched infants, taken as control. We found increased CD154 expression on both CD4+ and CD8+ lymphocytes in ART-treated infants, compared with the controls. CD154 was apparently functional, because the expression of CD86 on monocytes was enhanced; moreover, inhibition of the CD40-CD40L interaction produced downmodulation of CD86. From these results, we conclude that CD4+ and CD8+ lymphocytes of HIV-exposed noninfected infants, who have been exposed to antiretroviral drugs in fetal and early life, display enhanced CD154 expression and costimulatory activity.
authors.affiliation: Department of Biochemistry and Medical Biotechnologies, Federico II Medical School, Naples University, Naples, Italy. romano@dbbm.unina.it
authors.forename: Maria Fiammetta
authors.initials: MF
authors.lastname: Romano
authors.forename: Wilma
authors.initials: W
authors.lastname: Buffolano
authors.forename: Rita
authors.initials: R
authors.lastname: Bisogni
authors.forename: Rosario
authors.initials: R
authors.lastname: Russo
authors.forename: Raffaele
authors.initials: R
authors.lastname: Liuzzi
authors.forename: Madeleine
authors.initials: M
authors.lastname: Bunders
authors.forename: Marie Louise
authors.initials: ML
authors.lastname: Newell
authors.forename: Patrizia Carandente
authors.initials: PC
authors.lastname: Giarrusso
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control* / Q000635:transmission / Q000821:virology; D006679:HIV Seropositivity / Q000188:drug therapy*; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008297:Male; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
chemical_list: D012367:RNA, Viral; D023201:CD40 Ligand