CD8+ T cell-mediated suppression of HIV long terminal repeat-driven gene expression is not associated with improved clinical status

• Published in: AIDS (London) Vol. 11; no. 5; pp. 581 - 586
• Main Authors: COPELAND, K. F. T, LEITH, J. G, MCKAY, P. J, KELLEHER, L, SMAILL, F. M, ROSENTHAL, K. L
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.04.1997
• Subjects: AIDS/HIV; Biological and medical sciences; CD4-CD8 Ratio; CD8-Positive T-Lymphocytes - immunology; Cells, Cultured; Cytotoxicity, Immunologic; Gene Expression Regulation, Viral; HIV Infections - immunology; HIV Infections - physiopathology; HIV Long Terminal Repeat - genetics; HIV-1 - genetics; human immunodeficiency virus; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Medical sciences; Prognosis; Human; Immunopathology; Cell culture; Pathogenesis; AIDS; Cellular immunity; Gene expression; Immune deficiency; In vitro; Infection; Numeration; Clinical stage; Viral disease; T-Lymphocyte; Inhibition; LTR sequence
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/00002030-199705000-00005

To determine the associations between the suppression of HIV-1 long terminal repeat (LTR)-mediated gene expression by CD8+ T-cell supernatants and clinical correlates of well-being, including CD4+ and CD8+ T-cell counts, beta-chemokine production and clinical stage of disease. Culture supernatants of activated CD8+ T cells derived from a panel of HIV-1-infected subjects were assessed for their ability to suppress HIV-1 LTR-mediated chloramphenicol acetyl transferase (CAT) expression. The percentage suppression of gene expression was correlated with CD4+ and CD8+ T-cell counts and clinical stage of infection. Some individuals within this group were followed at 2-3 month intervals over time to assess the consistency of the suppression. Selected CD8+ T-cell culture supernatants of diverse suppressive ability were screened for the levels of the beta-chemokines macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta and RANTES. The ability of CD8+ T cells of HIV-1 infected subjects to suppress HIV-1 LTR-mediated gene expression did not show a dependence upon high CD4+ T-cell counts or on the clinical stage or duration of infection. The ability to suppress gene expression did show a relationship with higher CD8+ T-cell counts and correlated with the levels of beta-chemokines in the culture supernatants. In contrast, strong suppression was mediated by CD8+ T-cell supernatants from some subjects with very low CD8+ T-cell counts and relatively low chemokine levels. Although the suppression of gene expression by CD8+ T-cell culture supernatants showed statistical correlation with beta-chemokine levels and with higher CD8+ T-cell count, no correlation could be found with correlates of clinical well-being.