title: PKAI as a potential target for therapeutic intervention.
abstract: We have mapped a molecular mechanism for the impaired T-cell function in HIV infection and common variable immunodeficiency (CVI). Protein kinase A type I (PKAI) has a key role as an inhibitor of immune function in T lymphocytes and is activated following antigen receptor triggering. T cells from patients with HIV infection and CVI have increased activation of PKAI. This inhibits immune function and proliferation of T cells. Selective antagonists that block cAMP action through PKAI improve the immune function of T cells from HIV-infected patients up to 300%. Furthermore, combination of cAMP antagonists with interleukin-2 normalized immune responses of T cells from all patients examined and stimulated immune function of T cells from HIV-infected patients up to 600%. In addition, in vitro experiments indicate that approximately 50% of patients with CVI have a T-cell dysfunction that might benefit from a treatment reversing PKAI hyperactivation. This outlines PKAI as a potentially attractive drug target for immunomodulating therapy in HIV infection, as well as for the treatment of other immunodeficiency disorders such as CVI.
authors.affiliation: Institute of Medical Biochemistry, University of Oslo, Blindern, Oslo, Norway.
authors.forename: K
authors.initials: K
authors.lastname: Taskén
authors.forename: V
authors.initials: V
authors.lastname: Hansson
authors.forename: P
authors.initials: P
authors.lastname: Aukrust
authors.forename: S
authors.initials: S
authors.lastname: Frøland
authors.forename: B S
authors.initials: BS
authors.lastname: Skålhegg
authors.forename: F
authors.initials: F
authors.lastname: Müller
authors.forename: D
authors.initials: D
authors.lastname: Tobin
authors.forename: T
authors.initials: T
authors.lastname: Vang
authors.forename: K M
authors.initials: KM
authors.lastname: Torgersen
authors.forename: E M
authors.initials: EM
authors.lastname: Aandahl