PROTEIN-KINASE-A TYPE-I ANTAGONIST RESTORES IMMUNE-RESPONSES OF T-CELLS FROM HIV-INFECTED PATIENTS

Cyclic AMP-dependent protein kinase A (PKA) type I has been establishe d as an acute inhibitor of T cell activation. For this reason, we inve stigated the possible role of PKA. type I in HIV-induced T cell dysfun ction, T cells from HIV-infected patients have increased levels of cAM P and are more sensitive to inhibition by cAMP analog than are normal T cells. A PKA type I-selective antagonist increases the impaired prol iferation of T cells from HIV-infected patients to normal or subnormal levels (up to 2.8-fold). Follow-up of patients after initiation of hi ghly active antiretroviral treatment revealed that a majority of patie nts have a persistent T cell dysfunction that is normalized by incubat ion of T cells with Rp-8-Br-cAMPS, These observations imply that incre ased activation of PKA. type I may contribute to the progressive T cel l dysfunction in HIV infection and that PKA. type I may be a potential target for immunomodulating therapy.-Aandahl, E. M., Aukrust, P., Ska lhegg, B. S., Muller, F., Froland, S. S., Hansson, V., Tasken, K. Prot ein kinase A type I antagonist restores immune responses of T cells fr om HIV-infected patients.