T cell survival/proliferation reconstitution by trifluoperazine in human immunodeficiency virus-1 infection.
Recent findings support an indirect relationship between T cell depletion in HIV-1 infection and the rate of virus replication with implications for treatment strategies. We have initiated a new approach to recover immune function through the use of novel chemical agents. A cationic amphiphilic drug that binds to Ca(2+)-calmodulin at high concentrations, [10-[3-(4-methyl-1-piperazinyl)-propyl]-2- (trifluoromethyl)-(10)H-phenothiazine dihydrochloride] [denoted trifluroperazine dihydrochloride (Tfp); molecular weight 480.43] TFP was found at low concentrations (10(-6) to 10(-10) M) to help T cells from AIDS patients to restore proliferation in vitro. Here we show that the Tfp molecule can restore the cell survival of T lymphocytes from PBMCs derived from HIV-1-infected patients in vitro. Tfp enhances T cell proliferation and Th-cell responses by selectively inhibiting cell mortality and apoptosis. The restored antigen-specific response is associated with the synthesis of IL-2 and gamma-interferon. Even though this drug does not possess any detectable antiviral effect, it might be considered as a potential therapeutic agent in HIV-infected patients, to correct immune defects. Besides antiviral compounds, these data may facilitate immune reconstitution in patients with HIV infection and other immunosuppressive diseases.
Laboratore d'Oncologie et Virologie Moleculaires, Faculté de Médecine Necker, Centre Biomédical des Saint Pères, 75270 Paris, France. ammar.achour@wanadoo.fr
Ammar
A
Achour
Wei
W
Lu
Marine
M
Arlie
Li
L
Cao
Jean-Marie
JM
Andrieu
D017209:Apoptosis; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D014268:Trifluoperazine / Q000494:pharmacology* / Q000627:therapeutic use; D019562:Viral Load
D019394:Ki-67 Antigen; D012367:RNA, Viral; D014268:Trifluoperazine