The majority of individuals infected with M.tuberculosis achieve lifelong containment of4 the bacillus. What constitutes this effective host immune response is poorly understood.
We compared frequencies of IFN-γ-secreting T-cells specific for 5 Region-of-Difference-1-encoded antigens and 1 DosR-encoded antigen in 205 individuals with either active disease (n=167), whose immune responses had failed to contain the bacillus, or with presumed non-recent latent infection (n=38), who had successfully achieved immune control, and a further 149 individuals with recently acquired latent infection.
Amongst subjects with an IFN-γ ELISpot response to one or more RD1-encoded antigens, T-cells from subjects with active disease recognised more peptide pools from those antigens than did subjects with non-recent latent infection (P=0.002). T-cell frequencies to peptide pools were greater in active than non-recent latent infection for summed RD1 peptide pools (P≤0.006), and CFP-10 antigen (P=0.029). Individuals with recently (6 months) latent infection did not differ in numbers of peptide pools recognised, proportions recognising any individual antigen or
peptide pool, or antigen-specific T-cell frequencies (P≥0.11). The hierarchy of immunodominance across different antigens was PPD>CFP-10>ESAT- 6>Rv3879c>Rv3878>Rv3873>Acr1, being very similar between active and non-recent latent infection. Responses to the DosR antigen α-crystallin were not associated with latency (P=0.373). In contrast to RD1-specific responses, responses to PPD were not associated with clinical status (P>0.17) but were strongly associated with positive tuberculin skin test results (≥15mm induration, P≤0.01).
Our results suggest RD1-specific IFN-γ-secreting T-cell frequencies correlate with presence of disease rather than with protective immunity in M.tuberculosis-infected individuals and do not distinguish recently-acquired asymptomatic infection from remotely-acquired latent infection