T Cell Effector and Regulatory Subsets, Differentiating Between Active and Latent MTB Infection

Abstract

Last generation IFN gamma – based assays (IGRAs) evaluate bulk CD4 and CD8 T cell responses, and do not discriminate between latent and active Micobacterium tuberculosis (MTB) infection. The identification of biomarkers predicting the clinical course and specific therapy effect in latent MTB infection (LTBI) is a major contemporary challenge.
 Using multicolor flow cytometry, we compared the levels of circulating CD8 and CD4 effector subsets, in relation to the levels of phenotypically defined regulatory subsets, in two groups of age- and sex-matched MTB-infected individuals: clinically and microbiologically confirmed ATB (n=15), and QFT+ stable LTBI (n=15).
 As compared to LTBI subjects, ATB patients are characterized with decreased proportions of CD4 and CD8 CD45RO+CCR7- effectors (14.6% vs. 24%, and 28% vs. 40%, p <0.05 for both), decreased Th1 (10% vs. 16,5 %) and Th1/Th17 (12,5% vs. 21,5%) effector subsets. These changes are accompanied by a significantly increased share of induced (CD39+) FoxP3+CD4Treg (46% vs. 22.6%, p<0.05). The difference affected mostly the Th17-specific (CD39+CCR6+Treg) subset (10.5% vs 4.8%, p<0.05), which correlated inversely with the level of Th1/Th17 effectors (R= -0.5, p<0.05).
 In conclusion, we describe a clear-cut distinction between the effector/ regulatory T subset balance in ATB and LTBI. The combined evaluation of Th17Treg and Th1/Th17 effectors in peripheral blood can be employed for MTB-infection monitoring.
 ACKNOWLEDGMENTS: This work was supported by the Bulgarian National Science Fund (Research Grant ДН 13/1; 14.12.2017)