title: Cellular immune responses in human immunodeficiency virus (HIV)-1-infected children: is immune restoration by highly active anti-retroviral therapy comparable to non-progression?
abstract: The objective of this study was to investigate whether the restored immune functions of vertically human immunodeficiency virus (HIV)-infected children who were severely immunodeficient before the initiation of highly active anti-retroviral therapy (HAART) are comparable to those of untreated slow progressors. We therefore assessed T cell proliferation and cytokine [interferon (IFN)-γ, interleukin (IL)-5 and IL-13] secretions after mitogen, recall antigens and HIV-1-specific stimulation in 12 untreated slow progressors, 16 untreated progressors and 18 treated patients. Treated children were profoundly immunodeficient before the initiation of HAART and had long-lasting suppression of viral replication on treatment. We demonstrated that slow progressors are characterized not only by the preservation of HIV-1-specific lymphoproliferative responses but also by the fact that these responses are clearly T helper type 1 (Th1)-polarized. Children on HAART had proliferative responses to HIV-1 p24 antigen, purified protein derivative (PPD) and tetanus antigen similar to slow progressors and higher than those of progressors. However, in contrast to slow progressors, most treated children exhibited a release of Th2 cytokines accompanying the IFN-γ secretion in response to the HIV-1 p24 antigen. Moreover, despite higher proliferative responses to phytohaemagglutinin (PHA) than the two groups of untreated children, treated children had lower levels of IFN-γ secretion in response to PHA than slow progressors. These data show that in severely immunodeficient vertically HIV-infected children, a long-lasting HAART allows recovering lymphoproliferative responses similar to untreated slow progressors. However, alterations in IFN-γ secretion in response to the mitogen PHA persisted, and their cytokine release after HIV-specific stimulation was biased towards a Th2 response.
authors.affiliation: Department of Pediatrics, CHU Saint-Pierre, Hôpital Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium. marc_hainaut@stpierre-bru.be
authors.forename: M
authors.initials: M
authors.lastname: Hainaut
authors.forename: V
authors.initials: V
authors.lastname: Verscheure
authors.forename: M
authors.initials: M
authors.lastname: Ducarme
authors.forename: L
authors.initials: L
authors.lastname: Schandené
authors.forename: J
authors.initials: J
authors.lastname: Levy
authors.forename: F
authors.initials: F
authors.lastname: Mascart
mesh_terms: D000293:Adolescent; D023241:Antiretroviral Therapy, Highly Active; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D016207:Cytokines; D018572:Disease-Free Survival; D005260:Female; D016655:HIV Core Protein p24 / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000635:transmission*; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D008213:Lymphocyte Activation; D008297:Male; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D058408:Th1-Th2 Balance; D055815:Young Adult
chemical_list: D016207:Cytokines; D016655:HIV Core Protein p24; C514799:p24 protein, Human Immunodeficiency Virus Type 1