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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Copeland
K F
KF
Molecular Virology and Immunology Programme, McMaster University, Hamilton, Ontario, Canada.
Leith
J G
JG
McKay
P J
PJ
Kelleher
L
L
Smaill
F M
FM
Rosenthal
K L
KL
D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000276:immunology* / Q000503:physiopathology; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D011379:Prognosis