Effects of BCG vaccination on donor unrestricted T cells in humans

Gela, A.; Murphy, M.; Hadley, K.; Hanekom, W.; Boom, H.; Johnson, J.; Hoft, D.; Joosten, S.; Ottenhoff, T.; Suliman, S.; Moody, B.; Lewinsohn, D.; Hatherill, M.; Seshadri, C.; Nemes, E.; Scriba, T.

doi:10.1101/2021.04.29.441927

bioRxiv · 10.1101/2021.04.29.441927

Effects of BCG vaccination on donor unrestricted T cells in humans

Gela, A.·Murphy, M.·Hadley, K.·Hanekom, W.·Boom, H.·Johnson, J.·Hoft, D.·Joosten, S.·Ottenhoff, T.·Suliman, S.·Moody, B.·Lewinsohn, D.·Hatherill, M.·Seshadri, C.·Nemes, E.·Scriba, T.

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Abstract

Antigen classes other than proteins can be presented to T cells by near-monomorphic antigen-presenting molecules such as CD1, MR1, and butyrophilin 3A1. We sought to define the roles of donor unrestricted T (DURT) cells, including MR1-reactive MAIT cells, CD1b-reactive glucose monomycolate (GMM)-specific T cells, CD1d-reactive NKT cells, and {gamma}{delta} T cells, in vaccination against Mycobacterium tuberculosis. We characterized DURT cells following primary bacille Calmette-Guerin (BCG) vaccination in infants or BCG-revaccination in adults. BCG (re)vaccination did not modulate peripheral blood frequencies, T cell activation or memory profiles of MAIT cells, CD1b-restricted GMM-specific and germline-encoded mycolyl-reactive (GEM) cells or CD1d- restricted NKT cells. By contrast, BCG vaccination was associated with increased frequencies of {gamma}{delta} T cells as well as a novel subset of IFN-{gamma}-expressing CD4+ T cells with a CD26+CD161+TRAV1-2- phenotype in infants. More studies are required to understand the full potential of DURT cells in new TB vaccine strategies.

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Gela, A., Murphy, M., Hadley, K., Hanekom, W., Boom, H., Johnson, J., Hoft, D., Joosten, S., Ottenhoff, T., Suliman, S., Moody, B., Lewinsohn, D., Hatherill, M., Seshadri, C., Nemes, E., Scriba, T.. 2021-04-29. Effects of BCG vaccination on donor unrestricted T cells in humans. https://doi.org/10.1101/2021.04.29.441927

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