Mycobacterium tuberculosis exploits the CD95/CD95 ligand system of γδ T cells to cause apoptosis

Angelo A. Manfredi, Silvia Heltai, Patrizia Rovere, Clara Sciorati, Clara Paolucci, Giacomo Galati, Claudio Rugarli, Roberto Vaiani, Emilio Clementi, Marina Ferrarini

Research output: Contribution to journalArticlepeer-review


Vγ9/Vδ2+ T cells specifically recognize Mycobacterium tuberculosis in vitro and are precociously recruited in early mycobacterial lesions. Even if γδ T cells are only fortuitously detected in granulomas or bronchoalveolar lavages of patients with active pulmonary tuberculosis, a role in shaping the mature αβ T cell response against M. tuberculosis is substantiated. Here we provide a molecular explanation for this paradox: the engagement of the γδ TCR by mycobacterial antigens induced the expression of CD95 ligand (CD95L) by chronically activated CD95+/CD95L- γδ T lymphocytes. The receptor was functional, as CD95/CD95L interaction triggered the bystander death of CD95+ cells by apoptosis. Cell death was abolished by CD95-blocking antibodies. The transient accumulation at the site of infection of CD95L+ γδ lymphocytes, capable of interacting with CD95+ leukocytes attracted by the response towards the pathogen, may determine the characteristics of the ensuing granulomatous disease.

Original languageEnglish
Pages (from-to)1798-1806
Number of pages9
JournalEuropean Journal of Immunology
Issue number6
Publication statusPublished - Jun 1998


  • γδ T cell
  • Apoptosis
  • CD95
  • Fas
  • Macrophage
  • Tuberculosis

ASJC Scopus subject areas

  • Immunology


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