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(The FASEB Journal. 1998;12:855-862.)
© 1998 FASEB

RESEARCH COMMUNICATION

Protein kinase A type I antagonist restores immune responses of T cells from HIV-infected patients

Einar Martin Aandahla, Pål Aukrustb,c, Bjørn S. Skålhegga, Fredrik Müllerb,c, Stig S. Frølandb,c, Vidar Hanssona, and Kjetil Taskéna,1

a Institute of Medical Biochemistry, University of Oslo, N-0317 Oslo, Norway
b Research Institute for Internal Medicine, University of Oslo, N-0317 Oslo, Norway
c Section for Clinical Immunology and Infectious Diseases, Medical Department A, The National Hospital, N-0027 Oslo, Norway

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., Frøland, 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)


Key Words: cAMP • PKA • AIDS • Rp-8-Br-cAMPS




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