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., Skålhegg, B. S., Müller F., Fr⊘land, S. S., Hansson, V., Taskén, K., Protein kinase A type I antagonist restores immune responses of T cells from HIV‐infected patients. FASEB J . 12, 855–862 (1998)