Hadida F, Vieillard V, De Maeyer E, Baggiolini M, Autran B, Debre P; Hopital Pitie-Salpetriere, Paris, France.
Rantes and IFNb are immune mediators which have distinct antiviral activities against HIV. To combine antiviral therapy with an immune based intervention as a novel therapeutic approach to AIDS, we studied the effects of Rantes and IFNb on HIV specific T cell cytotoxicity. We found that Rantes makedly enhanced T cell cytotoxicity while such activity was abolished by an antibody neutralizing Rantes or a Rantes agonist. The effect of Rantes on CTL activity was abrogated by an antibody that blocks CCR3 indicating that specific lysis is triggered via this chemokine receptor. We when studied the effect of IFNb transduction on HIV specific CD8 T cells. IFNb transduced cells showed markely increased HIV specific MHC class I, restricted CTL activity against HIV. This effect was mediated by over expression of Rantes in CD8T cells. These observations 1) reveal a novel mechanisism of induction of specific cytotoxicity that depend on Rantes activity via CCR3, 2) present evidence that IFN b enhances cytotoxic activity by inducing an over production of Rantes, and 3)under score the possibility of the suggested combination therapy as a novel model of immunointervention in AIDS.
Keywords: AEGIS, T-Lymphocytes, Cytotoxic, RANTES, HIV, HIV-1, HIV Infections, Receptors, Chemokine, Antigens, CD8, T-Lymphocytes, Fenfluramine, HIV Antigens, Acquired Immunodeficiency Syndrome, Major Histocompatibility Complex, HIV Long Terminal Repeat, benfluorex, immunology, genetics, AIDS
