The Frequencies of IFNγ+IL2+TNFα+ PPD-Specific CD4+CD45RO+ T-Cells Correlate with the Magnitude of the QuantiFERON® Gold In-Tube Response in a Prospective Study of Healthy Indian Adolescents

“…M.tb-specific cytokineproducing CD4 T cells detected in reverters were of intermediate magnitude that fell between those observed in non-converters and persistent QFT+. These results are not consistent with findings by Jenum and colleagues, who reported that magnitude and cytokine co-expression profile of M.tbspecific Th1 CD4 T cells were not significantly different between IGRA reverters (n=6) and IGRA+ individuals [n=14, (9)]. M.tbspecific T cell activation (HLA-DR expression), which is likely associated with in vivo bacterial load during recent infection and active tuberculosis disease (29,31,32,36), was very low and not significantly different across study groups.…”

“…These findings provide evidence that some individuals can spontaneously cure M.tb infection and gave rise to the hypothesis that reversion of immunodiagnostic test results may be associated with M.tb clearance. Reversion has been observed naturally (2,(6)(7)(8)(9)(10)(11)(12)(13)(14) and in association with antibiotic treatment (8,13,15,16). Furthermore, a recent Bacille Calmette-Guerin (BCG) revaccination trial in M.tb-uninfected adolescents demonstrated vaccine efficacy against sustained M.tb infection, which was associated with transient IGRA conversion followed by reversion (IGRA-!…”

“…While pulmonary, smear‐positive TB patients presented with lower M. tuberculosis ‐specific trifunctional CD4 + T cells as compared to smear‐negative TB patients in one study , in another study patients with multi‐focal tuberculous lymphadenitis exhibited higher IFN‐γ + TNF + IL‐2 + CD4 + T‐cell frequencies compared to patients with pulmonary TB disease . Intriguingly, it has recently been reported that Indian adolescents who displayed strong and persistent responses in the QFT whole blood assay had correspondingly higher frequencies of trifunctional CD4 + T cells in response to M. tuberculosis antigens in in vitro assays as compared to individuals who exhibited a strong initial QFT response but later reverted to a negative QFT . Thus, although additional work is required to establish the relationship between M. tuberculosis antigen burden and the quality of the CD4 + T‐cell response, these studies suggest a link between these phenomena.…”

“…Several studies have documented higher frequencies of polyfunctional cytokine responses in peripheral blood samples from patients with latent or successfully treated pulmonary TB, as compared to active TB. [22][23][24] Polyfunctional responses have also been reported from local sites of inflammation, such as from bronchoalveolar lavage, in individuals with latent TB. 25 Pathogenspecific polyfunctionality of T-cells has been proposed to be a marker of T-cell efficacy and immune protection, not only in TB infections but in other infections as well.…”