Differential skewing of donor-unrestricted and ?? T cell repertoires in tuberculosis-infected human lungs.

ABSTRACT: Unconventional T cells that recognize mycobacterial antigens are of great interest as potential vaccine targets against tuberculosis (TB). This includes donor-unrestricted T cells (DURTs), such as mucosa-associated invariant T cells (MAITs), CD1-restricted T cells, and ?? T cells. We exploited the distinctive nature of DURTs and ?? T cell receptors (TCRs) to investigate the involvement of these T cells during TB in the human lung by global TCR sequencing. Making use of surgical lung resections, we investigated the distribution, frequency, and characteristics of TCRs in lung tissue and matched blood from individuals infected with TB. Despite depletion of MAITs and certain CD1-restricted T cells from the blood, we found that the DURT repertoire was well preserved in the lungs, irrespective of disease status or HIV coinfection. The TCR? repertoire, in contrast, was highly skewed in the lungs, where it was dominated by V?1 and distinguished by highly localized clonal expansions, consistent with the nonrecirculating lung-resident ?? T cell population. These data show that repertoire sequencing is a powerful tool for tracking T cell subsets during disease.

SUBMITTER: Ogongo P 

PROVIDER: S-EPMC6934215 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature