Transcriptomic Analysis of CD4+ T Cells Reveals Novel Immune Signatures of Latent Tuberculosis

• Published in: The Journal of immunology (1950) Vol. 200; no. 9; pp. 3283 - 3290
• Main Authors: Burel, Julie G, Lindestam Arlehamn, Cecilia S, Khan, Nabeela, Seumois, Grégory, Greenbaum, Jason A, Taplitz, Randy, Gilman, Robert H, Saito, Mayuko, Vijayanand, Pandurangan, Sette, Alessandro, Peters, Bjoern
• Format: Journal Article
• Language: English
• Published: United States American Association of Immunologists 01.05.2018
• Subjects: c-Kit protein; CCR6 protein; CD4 antigen; CXCR3 protein; Epitopes; Immune response; Immunological memory; L-selectin; Lymphocytes; Lymphocytes T; Memory cells; Phenotypes; Ribonucleic acid; RNA; Single-cell protein; T cell receptors; Tuberculosis
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.1800118

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−) 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−GPA33− 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.