AEGiS-11IAC: HIV-1 suppressive activity from transformed CD8 cells efficiently inhibits virus activation.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

HIV-1 suppressive activity from transformed CD8 cells efficiently inhibits virus activation.

Int Conf AIDS 1996 Jul 7-12; 11:439 (abstract no. Pub.A.1012)
Mosoian A, Piwoz J, Klotman ME; Mt. Sinai School of Medicine, New York, NY, USA.

The existence of soluble antiviral activity in CD8+ lymphocytes (CAF) was first reported several years ago by Levy and co-workers. To further study this activity, we have recently isolated a number of transformed (with Herpesvirus Saimiri, HVS), purified CD8+ cells from a cohort of pediatric long-term survivors and rapid progressors. To gain insight into the mechanism(s) of inhibition, we studied the antiviral activity of supernatant in an acute infection assay and in the chronically infected monocytic cell line, U1.

METHODS: Mixed PBMC from infected donors were infected with HVS strain C-488 following PHA stimulation. Surviving cells were further purified by limiting dilution and phenotyped by FACS. Purified populations of CD8+/CD3+ cells were analyzed for CAF activity utilizing an acute infection assay as originally described by Levy. Following one hour of infection with either HIV-1 strains IIIB, MN, Ba-1 or a primary isolate, cells were cultured in complete RPMI with IL-2 or supernatant from HVS-transformed CD8+ cells. Culture supernatants were obtained for HIV p24 antigen determination. We tested the ability of CAF from our cell lines to inhibit activation of HIV in the chronically infected U1 cell line (10). Cells were activated with PMA and cultured in the presence of CD8+ supernatant or complete media.

RESULTS: Suppressor activity was found in purified CD8+ cells from both rapid progressors as well as long-term survivors. Supernant from CD8+ cells from one donor was further analyzed and found to have significant HIV-1 inhibitory activity. There was greater than 95% inhibition of HIV-1IIIB at day 4 in the acute infection assay. The CD8+ cells were 92%-99% CD8+/CD3+. There was significant inhibitory activity in both primary and transformed CD4+ cells, and against a number of isolates including HIV-1MN, HIV-1 Ba-1 and a primary isolate. CAF inhibited activation of HIV in U-1 cells with an 83% inhibition at peak activation. Inhibition of activation could be seen as early as 21 hrs following activation.

CONCLUSION: HVS-transformed CD8+ cells from HIV-1 infected individuals exhibit significant and broad antiviral activity. Furthermore, CAF inhibits activation of HIV-1 in a chronically infected cell line consistent with its proposed mechanism of action on viral transcription. The relationship of this CAF activity to recently described chemokines and cytokines remains unknown.

Keywords: AEGIS, HIV-1, Antigens, CD8, Virus Activation, CD8-Positive T-Lymphocytes, HIV Long Terminal Repeat, HIV Infections, HIV, HIV Core Protein p24, Herpesvirus 2, Saimiriine, Anti-HIV Agents, HIV Long-Term Survivors, Antigens, CD3, Cell Line, HIV Seropositivity, Child, virology, genetics, ICA11

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PubA1012