title: T-cell death by apoptosis in vertically human immunodeficiency virus-infected children coincides with expansion of CD8+/interleukin-2 receptor-/HLA-DR+ T cells: sign of a possible role for herpes viruses as cofactors?
abstract: One mechanism proposed to play a role in T-cell depletion in human immunodeficiency virus (HIV) infection is apoptosis (activation-induced cell death). We assessed whether apoptosis is related to activation of T cells in vivo and its possible triggers. DNA was extracted from peripheral blood mononuclear cells (PBMC) taken from 16 vertically HIV-infected children and 9 HIV-negative children born to HIV-positive mothers (controls) and tested by agarose gel electrophoresis for the presence of DNA fragments specific for apoptosis. Signs of apoptosis were found on in vitro culture of PBMC from 12 of 16 HIV-infected children, but not in PBMC from the nine controls. Eleven of the 12 HIV-infected children with apoptosis showed an elevated (> 15%) proportion of CD3+/HLA-DR+ cells. This was due to an increased proportion of CD8+/HLA-DR+ cells, as shown in 7 of 7 further tested patients. In none of the probands an increased (> 5%) proportion of IL-2 receptor expressing CD3+ cells was found. T cells undergoing apoptosis were preferentially of the CD8+ phenotype. Expansion of circulating CD8+/interleukin-2 receptor (IL-2R)-/HLA-DR+ T cells is known to occur during active infection with herpes viruses. To investigate the possible role of herpes viral coinfections for apoptosis in HIV infection, we focused on Epstein-Barr virus (EBV) as an example for a herpes virus usually acquired during childhood. In 10 of 12 patients with apoptosis, we found increased levels of EBV genome in PBMC and/or tissues, indicating active EBV replication. By contrast, no increased burden of EBV was found in the four HIV-infected patients without apoptosis or in the controls. Our data indicate that in children the occurrence of apoptosis in HIV infection is closely related to activation of CD8+ T cells. Furthermore, primoinfection with or reactivation of herpes viruses, such as EBV, may substantially contribute to such T-cell activation and the ensuing apoptosis. Additional studies are warranted to evaluate the contribution of herpes virus-triggered apoptosis to the T-cell loss leading to the acquired immunodeficiency syndrome.
authors.affiliation: Division of Immunology/Hematology, University Children's Hospital, Zurich, Switzerland.
authors.forename: R P
authors.initials: RP
authors.lastname: Lauener
authors.forename: S
authors.initials: S
authors.lastname: Hüttner
authors.forename: M
authors.initials: M
authors.lastname: Buisson
authors.forename: J P
authors.initials: JP
authors.lastname: Hossle
authors.forename: M
authors.initials: M
authors.lastname: Albisetti
authors.forename: J M
authors.initials: JM
authors.lastname: Seigneurin
authors.forename: R A
authors.initials: RA
authors.lastname: Seger
authors.forename: D
authors.initials: D
authors.lastname: Nadal
mesh_terms: D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D015658:HIV Infections / Q000151:congenital* / Q000276:immunology / Q000473:pathology; D006684:HLA-DR Antigens / Q000032:analysis; D006566:Herpesviridae Infections / Q000150:complications / Q000276:immunology*; D004854:Herpesvirus 4, Human; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D008213:Lymphocyte Activation; D015375:Receptors, Interleukin-2 / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000166:cytology*; D014412:Tumor Virus Infections / Q000150:complications
chemical_list: D006684:HLA-DR Antigens; D015375:Receptors, Interleukin-2