TY - JOUR
T1 - Transcriptomic analysis of CD4 + t cells reveals novel immune signatures of latent tuberculosis
AU - Burel, Julie G.
AU - Lindestam Arlehamn, Cecilia S.
AU - Khan, Nabeela
AU - Seumois, Grégory
AU - Greenbaum, Jason A.
AU - Taplitz, Randy
AU - Gilman, Robert H.
AU - Saito, Mayuko
AU - Vijayanand, Pandurangan
AU - Sette, Alessandro
AU - Peters, Bjoern
N1 - Funding Information:
This work was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health under Awards U19AI118626 and S10OD018499. J.G.B., C.S.L.A., A.S., and B.P. designed the experiments; J.G.B., C.S.L.A., and N.K. conducted the experiments and/or analyzed the data; G.S., J.A.G., and P.V. provided technical resources; R.T., R.H.G., and M.S. provided samples; A.S. and B.P. provided funding; J.G.B. and B.P. wrote the manuscript; and all authors edited the manuscript.
Publisher Copyright:
Copyright © 2018 by The American Association of Immunologists, Inc.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1800118
DO - 10.4049/jimmunol.1800118
M3 - Article
C2 - 29602771
AN - SCOPUS:85045937261
SN - 0022-1767
VL - 200
SP - 3283
EP - 3290
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -