Restoration of T-cell function in HIV infection by reduction of intracellular cAMP levels with adenosine analogues.
OBJECTIVE
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.
Center for Interdisciplinary Research in Immunology, UCLA School of Medicine.
B
B
Hofmann
P
P
Nishanian
T
T
Nguyen
M
M
Liu
J L
JL
Fahey
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000595:Amino Acid Sequence; D000946:Antigens, Fungal; D002176:Candida albicans / Q000276:immunology; D000242:Cyclic AMP / Q000378:metabolism*; D016048:Dideoxyadenosine / Q000494:pharmacology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry; D011494:Protein Kinases / Q000378:metabolism; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*
D000946:Antigens, Fungal; D009842:Oligopeptides; D016048:Dideoxyadenosine; C037642:kemptide; D000242:Cyclic AMP; D011494:Protein Kinases; D000241:Adenosine