Differential skewing of donor-unrestricted and [gamma[delta] T cell repertoires in tuberculosis-infected human lungs.

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From: Journal of Clinical Investigation(Vol. 130, Issue 1)
Publisher: American Society for Clinical Investigation
Document Type: Article
Length: 11,656 words
Lexile Measure: 1410L

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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 [gamma][delta] T cells. We exploited the distinctive nature of DURTs and [gamma][delta] 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 TCR[delta] 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[delta] repertoire, in contrast, was highly skewed in the lungs, where it was dominated by V[delta]1 and distinguished by highly localized clonal expansions, consistent with the nonrecirculating lung-resident [gamma][delta] T cell population. These data show that repertoire sequencing is a powerful tool for tracking T cell subsets during disease.

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Gale Document Number: GALE|A612694415