CD8⁺T Cell Supernatants of HIV Type 1-Infected Individuals Have Opposite Effects on Long Terminal Repeat-Mediated Transcription in T Cells and Monocytes

Abstract

CD8+ T lymphocytes of HIV-1-infected individuals can efficiently suppress HIV-1 replication in CD4+ T lymphocytes via soluble factors. We compared the effect of CD8+ T cell-derived supernatants on HIV-1 LTR-driven gene expression in T cells and monocytic cell lines. Our results demonstrate that CD8+ T cell supernatants that suppressed HIV-1 LTR-driven gene expression in Jurkat T cells significantly enhanced expression in Tat-activated U38 monocytic cells in the presence and absence of mitogenic stimulation. Examination of a panel of CD8+ T cell-derived supernatants form HIV-infected individuals demonstrated that the extent of enhancement of transcription in U38 cells was mirrored in most cases by a similar level of suppression of transcription in Jurkat T cells. In latently infected U1 cells treated with TNF-alpha, culture with CD8+ T cell supernatants markedly enhanced virus production. In addition, the percentage increase in the enhancement of HIV-1 LTR-driven CAT expression by CD8+ T cell supernatants correlated strongly (r = 0.911) with the level of p24 detected. The level of LTR-mediated gene expression in U38 cells was not influenced by rhMIP-1 alpha rhMIP-1 beta, or rhRANTES over a wide range of chemokine concentration. Treatment of CD8+ T cell supernatant with a combination of antibodies to these chemokines resulted in a further augmentation of LTR-mediated CAT expression in U38 cells. Taken together, these results demonstrate that CD8+ T cell suppressive factors may have opposite effects on HIV-1 LTR-driven gene expression and replication dependent on target cell type and further suggest that the beta-chemokines do not influence HIV-1 LTR-mediated gene expression in monocytic cells.

CD8+T cell-mediated enhancement of tumour necrosis factor-alpha (TNF-α) production and HIV-1 LTR-driven gene expression in human monocytic cells is pertussis toxin-sensitive

“…*Pertussis toxin (PT) was used at 10 ng/ml. combination of antibodies to these chemokines abrogate the enhancement of HIV-1 replication in monocytic cells [22]. In this current work we have demonstrated that the enhancement of LTR-mediated gene expression is sensitive to PT, indicating a G protein-coupled mechanism of activation.…”

“…We previously reported that while CD8 þ T cell supernatants suppress HIV-1 LTR-mediated gene expression in Jurkat T cells [18,19], an opposite effect was observed on gene expression in monocytic cells [22]. …”

“…We previously reported on the opposite effects of CD8 þ T cells on gene expression in T cells versus monocytic cells [22]. The enhancement of gene expression in monocytic cells treated with CD8 þ T cell culture supernatants correlated strongly with the corresponding level of suppression of gene expression in Jurkat T cells.…”

“…We previously demonstrated that CD8 þ T cell supernatants of HIV-1-infected subjects increased HIV replication in monocytic cells in a manner independent of the b-chemokines MIP-1a, MIP1b and RANTES [22]. It has been reported that signal transduction via the G-protein-coupled RANTES receptor is not required for the anti-viral function of the chemokine [13].…”

“…The enhancement of gene expression in monocytic cells treated with CD8 þ T cell culture supernatants correlated strongly with the corresponding level of suppression of gene expression in Jurkat T cells. Further, we have shown that in both monocytic cells [22] and T cells [23] the modulation of LTRmediated gene expression was not induced by the b-chemokines RANTES, macrophage inflammatory protein-1a (MIP-1a) or MIP-1b or by a combination of these chemokines. It was recently reported that the chemokines individually or in combination did not suppress replication of HIV-1 SF33 in CD4 þ T cells [24].…”