Quantitative and Qualitative Perturbations of CD8+ MAITs in Healthy Mycobacterium tuberculosis–Infected Individuals

Mikhail Pomaznoy, Rebecca Kuan, Mikaela Lindvall, Julie G. Burel, Grégory Seumois, Pandurangan Vijayanand, Randy Taplitz, Robert H. Gilman, Mayuko Saito, David M. Lewinsohn, Alessandro Sette, Bjoern Peters, Cecilia S. Lindestam Arlehamn

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

CD8 T cells are considered important contributors to the immune response against Mycobacterium tuberculosis, yet limited information is currently known regarding their specific immune signature and phenotype. In this study, we applied a cell population transcriptomics strategy to define immune signatures of human latent tuberculosis infection (LTBI) in memory CD8 T cells. We found a 41-gene signature that discriminates between memory CD8 T cells from healthy LTBI subjects and uninfected controls. The gene signature was dominated by genes associated with mucosal-associated invariant T cells (MAITs) and reflected the lower frequency of MAITs observed in individuals with LTBI. There was no evidence for a conventional CD8 T cell–specific signature between the two cohorts. We, therefore, investigated MAITs in more detail based on Vα7.2 and CD161 expression and staining with an MHC-related protein 1 (MR1) tetramer. This revealed two distinct populations of CD8+Va7.2+CD161+ MAITs: MR1 tetramer+ and MR1 tetramer-, which both had distinct gene expression compared with memory CD8 T cells. Transcriptomic analysis of LTBI versus noninfected individuals did not reveal significant differences for MR1 tetramer+ MAITs. However, gene expression of MR1 tetramer- MAITs showed large interindividual diversity and a tuberculosis-specific signature. This was further strengthened by a more diverse TCR-α and -b repertoire of MR1 tetramer- cells as compared with MR1 tetramer+. Thus, circulating memory CD8 T cells in subjects with latent tuberculosis have a reduced number of conventional MR1 tetramer+ MAITs as well as a difference in phenotype in the rare population of MR1 tetramer- MAITs compared with uninfected controls.

Original languageEnglish (US)
Pages (from-to)292-307
Number of pages16
JournalImmunoHorizons
Volume4
Issue number6
DOIs
StatePublished - Jun 1 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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