Transcriptomic analysis of CD4 + t cells reveals novel immune signatures of latent tuberculosis

Julie G. Burel, Cecilia S. Lindestam Arlehamn, Nabeela Khan, Grégory Seumois, Jason A. Greenbaum, Randy Taplitz, Robert H. Gilman, Mayuko Saito, Pandurangan Vijayanand, Alessandro Sette, Bjoern Peters

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

In the context of infectious diseases, cell population transcriptomics are useful to gain mechanistic insight into protective immune responses, which is not possible using traditional whole-blood approaches. In this study, we applied a cell population transcriptomics strategy to sorted memory CD4 T cells to define novel immune signatures of latent tuberculosis infection (LTBI) and gain insight into the phenotype of tuberculosis (TB)-specific CD4 T cells. We found a 74-gene signature that could discriminate between memory CD4 T cells from healthy latently Mycobacterium tuberculosis–infected subjects and noninfected controls. The gene signature presented a significant overlap with the gene signature of the Th1* (CCR6 + CXCR3 + CCR4 2 ) subset of CD4 T cells, which contains the majority of TB-specific reactivity and is expanded in LTBI. In particular, three Th1* genes (ABCB1, c-KIT, and GPA33) were differentially expressed at the RNA and protein levels in memory CD4 T cells of LTBI subjects compared with controls. The 74-gene signature also highlighted novel phenotypic markers that further defined the CD4 T cell subset containing TB specificity. We found the majority of TB-specific epitope reactivity in the CD62L 2 GPA33 2 Th1* subset. Thus, by combining cell population transcriptomics and single-cell protein-profiling techniques, we identified a CD4 T cell immune signature of LTBI that provided novel insights into the phenotype of TB-specific CD4 T cells. The Journal of Immunology, 2018, 200: 3283–3290.

Original languageEnglish
Pages (from-to)3283-3290
Number of pages8
JournalJournal of Immunology
Volume200
Issue number9
DOIs
Publication statusPublished - 2018 May 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Transcriptomic analysis of CD4 <sup>+</sup> t cells reveals novel immune signatures of latent tuberculosis'. Together they form a unique fingerprint.

Cite this