Modulation of CD4 and CD8 response to QuantiFERON-TB-Plus in active TB patients followed during treatment

Introduction: The new IGRA called QuantiFERON-TB Plus (QFT-Plus), is based on the ELISA detection of IFNγ after stimulation with M. tuberculosis TB1 and TB2 antigens. We recently showed that while TB1 elicits mainly a CD4 response, the TB2 induces both CD4 and CD8 responses. Aims: to characterize the CD4 and CD8 responses to QFT-Plus peptides in active TB at baseline and during treatment and to identify an immune correlate of therapy success. Methods: We enrolled 15 active TB patients. PBMC were stimulated with QFT-Plus antigens. Cytokine profile (IFNγ, TNFα, IL2) and phenotype (CD45RA, CD27) of CD4 and CD8 T-cells were characterized by FACS. Results: Eight are the patients currently available who completed therapy. CD4 responses to TB1 and TB2 did not change overtime. Differently, regarding the CD8 responses we found a higher number of TB2-responders then TB1 at enrolment [TB1: 1/8 (0.13%), TB2: 4/8 (50%) respectively]. Interesting, the number of CD8 responders to TB1 increased at the end of specific treatment [TB1: 3/8 (38%)] compared to enrolment. The analysis of the memory profile showed that the largest component of antigen-specific CD4 (65%) had a central memory (CM) phenotype at enrolment and during follow up. On the other hand, specific CD8, which were analyzed only at follow-up because almost absent at baseline, were characterized by a large component with naive phenotype (40%) and a minor component with CM (25%) features. Conclusions: This is the first report characterizing the CD4 and CD8 responses to QFT-Plus antigens by FACS in active TB overtime. The results, although preliminary, may help in identifying immune correlate of therapy success.