title: Reconstitution of CD4+ T cell responses in HIV-1 infected individuals initiating highly active antiretroviral therapy (HAART) is associated with renewed interleukin-2 production and responsiveness.
abstract: Reconstitution of functional CD4(+) T cell responsiveness to in vitro stimuli is associated with continuous highly active antiretroviral therapy (HAART). Thirty-six antiretroviral naive patients received HAART over 16 weeks. Antigen-specific, mitogen and interleukin (IL)-2 induced lymphocyte proliferative responses and specific IL-2 and IL-4 production were assessed at each time-point, together with quantification of HIV-1 RNA load and lymphocyte populations. Reconstitution of recall responses was limited largely to persistent antigens such as Herpes simplex virus and Candida, rather than to HIV-1 or neo-antigens. Recall antigens, mitogens and IL-2-induced renewed responses were associated with in-vitro production of IL-2, but not IL-4. Differential responsiveness to low versus high concentration IL-2 stimulus increases in a stepwise manner, suggesting normalization of IL-2 receptor expression and improved functionality. These increases in in-vitro proliferative responses thus probably reflect short lived effector clones, driven by ongoing antigenic stimulus associated with persisting long-term organisms. In this context non-responsiveness to HIV-1 antigens suggests ongoing HIV-1 specific clonal T cell anergy.
authors.affiliation: Department of Immunology, Imperial College London, Chelsea and Westminster Hospital, London. g.hardy@imperial.ac.uk
authors.forename: G A D
authors.initials: GA
authors.lastname: Hardy
authors.forename: N
authors.initials: N
authors.lastname: Imami
authors.forename: A K
authors.initials: AK
authors.lastname: Sullivan
authors.forename: A
authors.initials: A
authors.lastname: Pires
authors.forename: C T
authors.initials: CT
authors.lastname: Burton
authors.forename: M R
authors.initials: MR
authors.lastname: Nelson
authors.forename: B G
authors.initials: BG
authors.lastname: Gazzard
authors.forename: F M
authors.initials: FM
authors.lastname: Gotch
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D017635:Clonal Anergy; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology; D018709:Statistics, Nonparametric; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D007376:Interleukin-2; D015847:Interleukin-4