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Innate and adaptive immune cell responses to recent M.tb infection

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posted on 12.05.2021, 13:10 by Tessa Lloyd, Cheleka Mpande, Elisa Nemes, Thomas Scriba, Virginie Rozot, Timothy Reid, Mark Hatherill, Boitumelo Mosito, Francesca Little, Pia Steigler, Constance Schreuder

This dataset includes meta data from the Adolescent Cohort Study (ACS) and innate and adaptive effector responses that were measured in stimulated Peripheral blood mononuclear cells (PBMCs). The risk of tuberculosis (TB) disease is higher in individuals with recent Mycobacterium tuberculosis (M.tb) infection compared to individuals with more remote, established infection. We aimed to define blood-based biomarkers to distinguish between recent and remote infection, which would allow targeting of recently infected individuals for preventive TB treatment.


PBMCs were collected at enrolment and at 6-monthly intervals during the 2-years of follow-up (termed months 0, 6, 12 and 18) when the QFT tests were performed to determine M.tb infection. Two groups of participants were defined based on their longitudinal QFT results: recent QFT converters (two consecutive QFT negative results, of which at least one is < 0.2 IU/mL, followed by another two consecutive QFT positive results, of which at least one is > 0.7 IU/mL) and persistent QFT positives (QFT positive results > 0.35 IU/mL at four consecutive visits). Overall, recent QFT converters and persistent QFT positives were matched by age, sex, ethnicity, school and known TB exposure.

Three stimulations were used to induce M.tb-specific T cell responses of the adaptive arm, including M.tb-specific peptide pools spanning ESAT-6/CFP-10 or EspC, EspF and Rv2348c (collectively termed Esp), and M.tb-lysate. The variables include a combination of 5 effector functions (IL2, TNF, IFNg, CD107, CD154) produced by CD4+ and CD8+ T cells upon stimulation. Combinations of the phenotypic markers CD45RA, CCR7, CD27, KLRG1, HLA-DR and CXCR3 were further measured on IFNg, IL2 or TNF producing T cells (total Th1).


In the innate dataset, effector responses were measured in unstimulated PBMC or after stimulation with M.tb-lysate. The variables in this dataset included a combination of 6 functional markers (Granzyme B, IL6, IL10, IL12, IFNg, TNF) produced by NK cells, B cells, monocytes, and DURT cells.


This dataset was used in the manuscript Multidimensional analysis of immune response identified biomarkers of recent Mycobacterium tuberculosis infection. See the full manuscript for more details.

Funding

Immunological significance of QuantiFERON TB Gold In-tube reversions in settings with high burden of tuberculosis

National Institute of Allergy and Infectious Diseases

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History

Department/Unit

South African Tuberculosis Vaccine Initiative