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 established as an acute inhibitor of T cell activation. For this reason, we investigated the possible role of PKA. type I in HIV-induced T cell dysfunction, T cells from HIV-infected patients have increased levels of cAMP and are more sensitive to inhibition by cAMP analog than are normal T cells. A PKA type I-selective antagonist increases the impaired proliferation of T cells from HIV-infected patients to normal or subnormal levels (up to 2.8-fold). Follow-up of patients after initiation of highly active antiretroviral treatment revealed that a majority of patients have a persistent T cell dysfunction that is normalized by incubation of T cells with Rp-8-Br-cAMPS, These observations imply that increased activation of PKA. type I may contribute to the progressive T cell dysfunction in HIV infection and that PKA. type I may be a potential target for immunomodulating therapy.-Aandahl, E. M., Aukrust, P., Skalhegg, B. S., Muller, F., Froland, S. S., Hansson, V., Tasken, K. Protein kinase A type I antagonist restores immune responses of T cells from HIV-infected patients.