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. Jul-Sep 2019;37(3):370-375.
doi: 10.4103/ijmm.IJMM_18_439.

Frequencies of Regulatory Subsets of CD4 + TH Cells in Peripheral Blood in Mycobacterium Tuberculosis-Infected Individuals and Healthy Contacts in a High-Burden Setting From Assam, Northeast India

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Frequencies of Regulatory Subsets of CD4 + TH Cells in Peripheral Blood in Mycobacterium Tuberculosis-Infected Individuals and Healthy Contacts in a High-Burden Setting From Assam, Northeast India

Lahari Saikia et al. Indian J Med Microbiol. .
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Abstract

Background: Mycobacterium tuberculosis (Mtb) adapts many strategies to persist and replicate inside human tissue. One such strategy is the manipulation of CD4+ TH cells for subset interconversion to regulatory subsets. The aim of the present study is to get an insight of dynamic changes of CD4+ TH cells to regulatory subsets, CD4+ CD25+ forkhead box P3 (Foxp3)+ T-cells and CD4+ CD25+ Foxp3+ programmed death molecule-1 (Foxp3+) T-cells, in peripheral blood in Mtb-infected individuals and healthy contacts in a high-burden setting from Assam, Northeast India.

Materials and methods: A case-control study was conducted in newly diagnosed active pulmonary tuberculosis (APTBs) patients and 2 sets of controls: (i) individuals infected with latent tuberculosis infection (LTBI) and (ii) healthy close tuberculosis healthy contacts (HCs). The frequencies of different subsets of CD4+ cells with regulatory markers were measured in peripheral blood in 3 groups of study participants.

Results and observations: Frequencies of CD4+ CD25+ Foxp3+ T-cells (1.84 ± 1.40 vs. 4.32 ± 1.82 vs. 11.30 ± 3.66), CD4+ CD25+ Foxp3+ PD1+ T-cells (0.37 ± 1.28 vs. 2.99 ± 3.69 vs. 14.54 ± 5.10) and ligand (PD-L1)-positive CD4+ TH cells (0.80 ± 0.45 vs. 2.28 ± 0.95 vs. 7.13 ± 2.02) were significantly increased from HCs to LTBIs to APTB patients, respectively (P < 0.0001). No significant changes in frequencies of total CD4+ cells were observed between APTBs (29.51 ± 11.93), LTBIs (29.23 ± 8.16) and HCs (28.16 ± 9.73) whereas the mean ratios of CD4+ to CD4+ CD25+ FoxP3+ were significantly decreased from 34.34 ± 47.56 in HCs to 7.96 ± 5.8 in LTBIs to 3.12 ± 2.58 in APTBs (P < 0.0001). Significant decrease in mean ratios of CD4+ CD25+ FoxP3+ to CD4+ CD25+ FoxP3+ PD1+ were also observed from 4.97 ± 1.09 in HCs to 1.44 ± 0.49 in LTBIs to 0.78 ± 0.72 in APTBs.

Conclusion: CD4+ TH cells change dynamically to regulatory subsets depending on the status of infection and a shift of response towards excessive regulatory T-cells, and PD-1/PD-L1 production may help in the development of active infection in latently infected individuals. These immunological parameters may be used, as potential biomarkers to see the changing dynamics of Mtb infection.

Keywords: CD4+TH cells; Treg cells; programmed death molecule-1/programmed death molecule ligand 1 pathway; tuberculosis.

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