AEGiS-11IAC: CD8 T lymphocyte-mediated suppression of HIV-1 LTR-mediated transcription shows no correlation with clinical stage of disease or health status.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

CD8 T lymphocyte-mediated suppression of HIV-1 LTR-mediated transcription shows no correlation with clinical stage of disease or health status.

Int Conf AIDS 1996 Jul 7-12; 11:227 (abstract no. Tu.A.395)
Copeland KF, Leith J, Kelleher L, Smaill F, Rosenthal KL; Dept. of Pathology, McMaster University, Hamilton, Ontario. Fax: (905) 521-2613.

OBJECTIVES: CD8+ T lymphocytes of HIV-1 infected individuals efficiently suppress HIV-1 replication in CD4+ Tcells and this suppression has been shown to correlate with high CD4+ T cell counts and lack of disease progression. This study examines the transcriptional control of HIV-1 LTR-mediated expression by CD8+ T cells and compares this activity with chemokine production by CD8+ cells and with clinical stage of disease.

METHODS: Human Jurkat T cells were transfected with a vector bearing the HIV-1 LTR directing the chloramphenicol acetyl transferase gene (CAT) and a vector expressing HIV-1 Tat. CAT activity was measured following culture of the transfected cells with supernatant of activated CD8+ T cells of HIV-infected subjects. The presence of RANTES in supernatants was measured by Elisa.

RESULTS: We have examined the ability of CD8+ T cell supernatants of patients of varied clinical stage to inhibit LTR-mediated gene transcription. Strong suppression of transcription was not restricted to asymptomatic subjects and in several cases subjects with AIDS were among the strongest suppressors of transcription. Similarly, low level suppressors included asymptomatic subjects and those who had progressed to AIDS. No correlation of CD8+ T cell-mediated suppressive activity could be found with CD4+ or CD8+ T cell counts, duration of infection or antiviral treatment. CD8+ T cell-mediated suppression was also noted in patients experiencing weight loss, Kaposi's sarcoma, pneumocystis carinii and oesophageal candidiasis. In some subjects followed longitudinally, the suppressive effects of CD8+ T cells varied dramatically between two-month sampling periods. In addition, the level of inhibition evoked by supernatants correlated with the amount of RANTES present in the supernatants. We will present data on the level of suppression of transcription by CD8+ T cell supernatants paired with the level of selected chemokines present in the supernatants. In addition, a comparison of the effect of CD8+ T cell-mediated suppression on virus replication and transcription will be presented.

CONCLUSION: Further investigation of CD8+ T cell-mediated suppression is required to determine its role in disease progression and its effect on other steps in the virus life cycle.

Keywords: AEGIS, HIV Long Terminal Repeat, Antigens, CD8, HIV-1, CD8-Positive T-Lymphocytes, Transcription, Genetic, Virus Replication, HIV Infections, RANTES, Chemokines, HIV, HIV Core Protein p24, HIV-1 Reverse Transcriptase, Cats, Animal, Human, genetics, virology, ICA11

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TuA395