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

FASEB J. 1998 Jul;12(10):855-62. doi: 10.1096/fasebj.12.10.855.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacology*
  • Carrier Proteins / pharmacology*
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors*
  • Female
  • HIV Infections / immunology*
  • HIV Infections / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Male
  • Middle Aged
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology

Substances

  • Anti-HIV Agents
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • protein kinase modulator
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases