T cell-derived suppressive activity: Evidence of autocrine noncytolytic control of HIV type 1 transcription and replication

Citation
Jg. Leith et al., T cell-derived suppressive activity: Evidence of autocrine noncytolytic control of HIV type 1 transcription and replication, AIDS RES H, 15(17), 1999, pp. 1553-1561
Citations number
55
Categorie Soggetti
Immunology
Journal title
AIDS RESEARCH AND HUMAN RETROVIRUSES
ISSN journal
08892229 → ACNP
Volume
15
Issue
17
Year of publication
1999
Pages
1553 - 1561
Database
ISI
SICI code
0889-2229(19991120)15:17<1553:TCSAEO>2.0.ZU;2-G
Abstract
The ability of CD8(+) T lymphocytes to suppress the transcription and repli cation of HIV-1 is well documented. We have demonstrated that the factor(s) responsible for the suppression of HIV-1 LTR-mediated gene expression are not the CC chemokines RANTES, MIP-1 alpha, and MIP-1 beta. Interestingly, t hese and other chemokines and cytokines are produced by both CD8(+) and CD4 (+) T lymphocytes. On the presumption that CD4(+) T lymphocytes may also be able to modulate HIV-1 expression in vitro we assessed the LTR-modulatory effects of a panel of culture supernatants derived from stimulated CD4(+) T lymphocytes from HIV-positive patients and uninfected controls. Supernatan ts of both CD4(+) and CD8(+) T cells mediated a suppression of LTR-driven g ene expression in Jurkat T cells and an enhancement of gene expression in U 38 monocytic cells. On the basis of these results, and using a herpesvirus saimiri (HVS)-transformed CD4(+) T lymphocyte clone (HVSCD4), we demonstrat e that both suppressive and enhancing effects are dose dependent. Furthermo re, we have shown that supernatants of both HVSCD4 and HVSCD8 cells suppres s LTR-mediated gene expression and HIV-1 replication in transfected/infecte d T cells, In U1 monocytic cells, supernatants of both CD4(+) and CD8(+) ly mphocytes from an HIV-1-infected individual enhanced LTR-mediated gene expr ession, HIV-1 replication, and TNF-alpha production. However, only these ef fects as induced by CD8(+) T cells were sensitive to the G protein inhibito r pertussis toxin. These results indicate that factors produced by both CD4 (+) and CD8(+) T cells exert dichotomous effects on HIV-1 gene expression a nd replication in T cells and monocytes.