Effects of BCG vaccination on donor unrestricted T cells in two prospective cohort studies
| Autor: | Gela, A., Murphy, M., Rodo, M., Hadley, K., Hanekom, W.A., Boom, W.H., Johnson, J.L., Hoft, D.F., Joosten, S.A., Ottenhoff, T.H.M., Suliman, S., Moody, D.B., Lewinsohn, D.M., Hatherill, M., Seshadri, C., Nemes, E., Scriba, T.J., Briel, L., Veldtsman, H., Khomba, N., Pienaar, B., Africa, H., Steyn, M., Delayed BCG Study Team |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Medicine (General) Unconventional T cells Vaccination Infant General Medicine Mycobacterium tuberculosis General Biochemistry Genetics and Molecular Biology Mucosal-Associated Invariant T Cells R5-920 Memory BCG Vaccine Medicine Humans Tuberculosis BCG Prospective Studies |
| Zdroj: | EBioMedicine, Vol 76, Iss, Pp 103839-(2022) EBioMedicine, 76. ELSEVIER |
| DOI: | 10.1016/j.ebiom.2022.103839 |
| Popis: | Summary: Background: Non-protein antigen classes can be presented to T cells by near-monomorphic antigen-presenting molecules such as CD1, MR1, and butyrophilin 3A1. Such T cells, referred to as donor unrestricted T (DURT) cells, typically express stereotypic T cell receptors. The near-unrestricted nature of DURT cell antigen recognition is of particular interest for vaccine development, and we sought to define the roles of DURT cells, including MR1-restricted MAIT cells, CD1b-restricted glucose monomycolate (GMM)-specific T cells, CD1d-restricted NKT cells, and γδ T cells, in vaccination against Mycobacterium tuberculosis. Methods: We compared and characterized DURT cells following primary bacille Calmette-Guerin (BCG) vaccination in a cohort of vaccinated and unvaccinated infants, as well as before and after BCG-revaccination in adults. Findings: 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, primary BCG vaccination was associated with increased frequencies of γδ T cells as well as a novel subset of CD26+CD161+TRAV1-2− IFN-γ-expressing CD4+ T cells in infants. Interpretation: Our findings, that most DURT cell populations were not modulated by BCG, do not preclude a role of BCG in modulating other qualitative aspects of DURT cells. More studies are required to understand the full potential of DURT cells in new TB vaccine strategies. Funding: Aeras, the National Institutes of Health, and the Bill and Melinda Gates Foundation. |
| Databáze: | OpenAIRE |
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