OBJECTIVE AND DESIGN: The impaired function of T cells is characteristic of HIV infection. It contributes to disease pathogenesis and is associated with disease prognosis. Our aim was to describe a biochemical basis for this impairment and a pharmacological way of restoring function. METHODS: Measurement of intracellular cAMP, protein kinase A (PKA) activity and proliferative capacity of T cells to recall antigens. RESULTS: HIV-seropositive individuals without AIDS showed significant increases in intracellular cAMP levels and PKA activity (inhibitors of lymphocyte function). The proliferative capacity of T cells to recall antigens correlated inversely with initial cAMP levels: poor proliferation was associated with high cAMP level in HIV infection. Moreover, drugs that reduced intracellular cAMP levels led to significant restoration of specific T-cell proliferation and cytotoxicity. CONCLUSIONS: Our findings indicate that high intracellular cAMP concentrations contribute to pathogenesis of T-cell anergy in HIV infection and that drugs that decrease intracellular cAMP levels may be beneficial in the treatment of AIDS.
OBJECTIVE AND DESIGN: The impaired function of T cells is characteristic of HIV infection. It contributes to disease pathogenesis and is associated with disease prognosis. Our aim was to describe a biochemical basis for this impairment and a pharmacological way of restoring function. METHODS: Measurement of intracellular cAMP, protein kinase A (PKA) activity and proliferative capacity of T cells to recall antigens. RESULTS:HIV-seropositive individuals without AIDS showed significant increases in intracellular cAMP levels and PKA activity (inhibitors of lymphocyte function). The proliferative capacity of T cells to recall antigens correlated inversely with initial cAMP levels: poor proliferation was associated with high cAMP level in HIV infection. Moreover, drugs that reduced intracellular cAMP levels led to significant restoration of specific T-cell proliferation and cytotoxicity. CONCLUSIONS: Our findings indicate that high intracellular cAMP concentrations contribute to pathogenesis of T-cell anergy in HIV infection and that drugs that decrease intracellular cAMP levels may be beneficial in the treatment of AIDS.
Authors: Jeffrey M Greeson; David R Gettes; Sergei Spitsin; Benoit Dubé; Tami D Benton; Kevin G Lynch; Steven D Douglas; Dwight L Evans Journal: Biol Psychiatry Date: 2015-11-10 Impact factor: 13.382
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Authors: Michelle J Farquhar; Helen J Harris; Mandy Diskar; Sarah Jones; Christopher J Mee; Søren U Nielsen; Claire L Brimacombe; Sonia Molina; Geoffrey L Toms; Patrick Maurel; John Howl; Friedrich W Herberg; Sven C D van Ijzendoorn; Peter Balfe; Jane A McKeating Journal: J Virol Date: 2008-06-25 Impact factor: 5.103