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.
Achour
Ammar
A
Laboratore d'Oncologie et Virologie Moleculaires, Faculté de Médecine Necker, Centre Biomédical des Saint Pères, 75270 Paris, France. ammar.achour@wanadoo.fr
Lu
Wei
W
Arlie
Marine
M
Cao
Li
L
Andrieu
Jean-Marie
JM
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