An abnormal phenotype of lung Vγ9Vδ2 T cells impairs their responsiveness in tuberculosis patients

• γδ T cells play an important role during early phases of MTB infection.
• BAC Vγ9Vδ2 T cells present a strong down modulation of CD3 expression compared with their counterpart in peripheral blood.
• BAC Vγ9Vδ2 T cells express different phenotype compared to circulating Vγ9Vδ2 T cells.
• Vγ9Vδ2 T cell functions are specifically impaired in situ by active TB.

Antigen-specific γδ T cells represent an early innate defense known to play an important role in anti-mycobacterial immunity. We have investigated the immune functions of Vγ9Vδ2 T cells from Broncho-Alveolar lavages (BAC) samples of active TB patients. We observed that BAC Vγ9Vδ2 T cells presented a strong down-modulation of CD3 expression compared with Vγ9Vδ2 T cells from peripheral blood. Furthermore, Vγ9Vδ2 T cells mainly showed a central memory phenotype, expressed high levels of NK inhibitory receptors and TEMRA cells showed low expression of CD16 compared to circulating Vγ9Vδ2 T cells. Interestingly, the ability of BAC Vγ9Vδ2 T cells to respond to antigen stimulation was dramatically reduced, differently from blood counterpart. These observations indicate that γδ T cell functions are specifically impaired in situ by active TB, suggesting that the alveolar ambient during tuberculosis may affect resident γδ T cells in comparison to circulating cells.