title: Immunological dysfunction in HIV-1-infected individuals caused by impairment of adenosine deaminase-induced costimulation of T-cell activation.
abstract: The cell surface association between CD26 and adenosine deaminase (ADA) has a costimulatory function during T-cell activation. Several studies have revealed correlations among CD4(+) CD26(+) T-cell depletion, increased serum levels of ADA, and the evolution of human immunodeficiency virus (HIV) infection, implicating CD26 and ADA in HIV disease progression. In this context, we aimed to determine whether ADA costimulation could be altered during HIV infection. ADA costimulation was investigated in cells from HIV-infected patients (n = 36) in terms of proliferation and cytokine secretion. An effect of ADA on T-cell proliferation was found in HIV-1-infected patients and correlated positively with the CD4(+) percentage and the nadir CD4 count and negatively with viral load, demonstrating that the response depends on the immunological status of the patient. The robust ADA-induced increase in cytokine production [interferon (IFN)-gamma, interleukin (IL)-6 and IL-10] was markedly reduced in T cells from HIV-1-infected subjects. To eliminate some of the variables associated with immunological defects in HIV-1-infected patients, anti-CD3 plus ADA assays with T cells from healthy volunteers were performed in the presence of recombinant glycoprotein 120 (gp120). It was found that gp120 was responsible for the impairment of the ADA-CD26 interaction and consequently of the ADA-induced effect on both costimulation and cytokine production. The gp120-mediated disruption of the CD26-ADA interaction is a novel mechanism that might explain, at least in part, the altered immunological features observed in HIV-1-infected patients and may have significant relevance in AIDS pathogenesis.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain. martinez-navio@ub.edu
authors.forename: José M
authors.initials: JM
authors.lastname: Martinez-Navio
authors.forename: Núria
authors.initials: N
authors.lastname: Climent
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Pacheco
authors.forename: Felipe
authors.initials: F
authors.lastname: Garcia
authors.forename: Montserrat
authors.initials: M
authors.lastname: Plana
authors.forename: Meritxell
authors.initials: M
authors.lastname: Nomdedeu
authors.forename: Harold
authors.initials: H
authors.lastname: Oliva
authors.forename: Cristina
authors.initials: C
authors.lastname: Rovira
authors.forename: Laia
authors.initials: L
authors.lastname: Miralles
authors.forename: José M
authors.initials: JM
authors.lastname: Gatell
authors.forename: Teresa
authors.initials: T
authors.lastname: Gallart
authors.forename: Josefa
authors.initials: J
authors.lastname: Mallol
authors.forename: Carme
authors.initials: C
authors.lastname: Lluis
authors.forename: Rafael
authors.initials: R
authors.lastname: Franco
mesh_terms: D000243:Adenosine Deaminase / Q000276:immunology / Q000378:metabolism*; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000276:immunology / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D015497:HIV-1 / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D019562:Viral Load
chemical_list: D016207:Cytokines; D015699:HIV Envelope Protein gp120; D018819:Dipeptidyl Peptidase 4; D000243:Adenosine Deaminase