Disease extent and anti-tubercular treatment response correlates with Mycobacterium tuberculosis-specific CD4 T-cell phenotype regardless of HIV-1 status

Whole blood-based assays of Mtb-specific CD4 T-cell activation and maturation markers can be used as non-sputum-based biomarkers of disease extent and treatment monitoring in TB, regardless of HIV-1 status.

Using flow cytometry, we measured the expression of phenotypic and functional markers (HLA-DR, CD27, CD153, KLRG1, IL-2, MIP-1β, TNF-α and IFN-γ) on Mtb-specific CD4 T-cells in whole blood from 161 participants of varying TB and HIV status. TB disease extent was graded as a continuum using the Xpertct value, C-reactive protein, Timika radiographic score and monocyte/lymphocyte ratio.

The phenotypic profile of Mtb-specific CD4 T cells pre-anti-tubercular treatment (ATT) strongly correlated with disease extent, irrespective of HIV status. ATT associated with major changes in the phenotype of Mtb-specific CD4 T cells, with decreased expression of HLA-DR and increased CD27 and CD153 expression. Principal component analysis showed an almost complete separation between latent TB infection (LTBI) and active TB (aTB) pre-ATT groups, whereas the profile of the aTB post-ATT group overlapped with the LTBI group. However, in patients experiencing treatment failure or relapse, no significant changes were observed in Mtb-specific CD4 T-cell phenotype pre- and post-ATT.