Double-edged effect of Vγ9/Vδ2 T lymphocytes on viral expression in an in vitro model of HIV-1/mycobacteria co-infection

Priscilla Biswas, Marina Ferrarini, Barbara Mantelli, Claudio Fortis, Guido Poli, Adriano Lazzarin, Angelo A. Manfredi

Research output: Contribution to journalArticlepeer-review


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 in acceleration of HIV disease progression. Vγ9/Vδ2 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-α and IFN-γ, which are also up-regulators of HIV expression. To assess whether mycobacteria-activated γδ T lymphocytes contribute to the enhancement of HIV replication, we established an in vitro model mimicking HIV and mycobacteria coinfection with the latently HIV-infected promonocytic U1 cell line and Vγ9/Vδ2 peripheral lymphocytes stimulated with mycobacterial Ag. γδ T cell activation determined two distinct, but connected effects, namely U1 cell death and HIV expression. Both effects were mainly mediated by release of TNF-α and IFN-γ from activated γδ 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 γδ cells. In particular, the induction of viral expression prevailed at low Ag concentration and with lower cytokine production by mycobacteria-activated γδ cells. Notably, during the course of HIV infection, Vγ9/Vδ2 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 γδ T cells were co-cultured with primary HIV-infected macrophages. Thus, we suggest that specific recognition of mycobacterial Ag by γδ T lymphocytes in co-infected individuals may modulate viral replication through the complex array of soluble factors released.

Original languageEnglish
Pages (from-to)252-263
Number of pages12
JournalEuropean Journal of Immunology
Issue number1
Publication statusPublished - Jan 1 2003


  • γδ T lymphocyte
  • Apoptosis
  • Cytokine
  • HIV
  • Mycobacteria

ASJC Scopus subject areas

  • Immunology


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