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

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posted on 25.06.2021, 13:12 by Tessa LloydTessa Lloyd, Cheleka MpandeCheleka Mpande, Elisa NemesElisa Nemes, Thomas ScribaThomas Scriba, Virginie RozotVirginie Rozot, Timothy Reid, Mark Hatherill, Boitumelo Mosito, Francesca LittleFrancesca Little, Pia SteiglerPia Steigler, Constance Schreuder

This dataset includes 4 excel spreadsheets consisting of meta data from the Adolescent Cohort Study (ACS) and innate and adaptive cellular 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.

Five 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; Staphylococcus Enterotoxin B (SEB), as a positive control; or the cells were left unstimulated as a negative control. 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 or E. Coli (positive control). 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.


Below is a brief description of the different spreadsheets in the dataset:

1.) Meta Data: Consists of the meta data from the study.

2.) Raw Data: Contains all the data that was generated from both the adaptive and innate panel. Variable values are reported as a percent of the parent cell population.

3.) CD4 and CD8 Counts: Consists of event counts for the CD4 and CD8 cell populations used for COMPASS and MIMOSA analyses.

4.) Filtered Data: Consists of only the variables included in the analysis. A filtering process was applied according to the criteria described in the paper, and variable values are background subtracted when appropriate.

5.) Dictionary: A summary of the two datasets and how the variable names were defined.


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