Double-edged effect of Vgamma9/Vdelta2 T lymphocytes on viral expression in an in vitro model of HIV-1/mycobacteria co-infection

A reciprocal influence exists between mycobacteria and HIV: HIV-infected individuals are more susceptible to mycobacterial infections and, on the other hand, mycobacterial infection results inacceleration of HIV disease progression. Vgamma9/Vdelta2 T lymphocytes are known to participate in the defen...

Full description

Saved in:
Bibliographic Details
Published in:European journal of immunology 2003-01, Vol.33 (1), p.252-263
Main Authors: Biswas, Priscilla, Ferrarini, Marina, Mantelli, Barbara, Fortis, Claudio, Poli, Guido, Lazzarin, Adriano, Manfredi, Angelo A
Format: Article
Language:English
Subjects:
Apoptosis
Cell Division
Cell Line
fas Receptor - metabolism
Flow Cytometry
Gene Expression Regulation, Viral
Hemiterpenes
HIV Infections - complications
HIV Infections - immunology
HIV Infections - virology
HIV-1 - genetics
HIV-1 - physiology
Humans
Interferon-gamma - metabolism
Models, Biological
Mycobacterium Infections - complications
Mycobacterium Infections - immunology
Organophosphorus Compounds - pharmacology
Receptors, Antigen, T-Cell - immunology
Receptors, Antigen, T-Cell - metabolism
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Tumor Necrosis Factor-alpha - metabolism
U937 Cells
Virus Replication
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A reciprocal influence exists between mycobacteria and HIV: HIV-infected individuals are more susceptible to mycobacterial infections and, on the other hand, mycobacterial infection results inacceleration of HIV disease progression. Vgamma9/Vdelta2 T lymphocytes are known to participate in the defense against intracellular pathogens, including Mycobacterium tuberculosis. Indeed, they kill mycobacteria-infected macrophages and, upon recognition of mycobacterial Ag, release TNF-alpha and IFN-gamma, which are also up-regulators of HIV expression. To assess whether mycobacteria-activated gamma delta T lymphocytes contribute to the enhancement of HIV replication, we established an in vitro model mimicking HIV and mycobacteria co-infection with the latently HIV-infected promonocytic U1 cell line and Vgamma9/Vdelta2 peripheral lymphocytes stimulated with mycobacterial Ag. gamma delta T cell activation determined two distinct, but connected effects, namely U1cell death and HIV expression. Both effects were mainly mediated by release of TNF-alpha and IFN-gamma from activated gamma delta lymphocytes, although Fas-FasL interaction also contributed to U1 apoptosis. The final outcome on U1 survival, and thus, on HIV expression, highly depended on mycobacterial Ag concentration coupled to the differential secretory potency of gamma delta cells. In particular, the induction of viral expression prevailed at low Ag concentration and with lower cytokine production by mycobacteria-activated gamma delta cells. Notably, during the course of HIV infection, Vgamma9/Vdelta2 lymphocytes are reported to be functionally impaired and may thus indirectly influence the progression of HIV disease. In addition, a predominant inhibition of viral replication was encountered when mycobacteria-activated gamma delta T cells were co-cultured with primary HIV-infected macrophages. Thus, we suggest that specific recognition of mycobacterial Ag by gamma delta T lymphocytes in co-infected individuals may modulate viral replication through the complex array of soluble factors released.
ISSN:0014-2980
1521-4141