Comparative immune responses to Mycobacterium tuberculosis in people with latent infection or sterilizing protection

Abstract

There is great need for vaccines against tuberculosis (TB) more efficacious thanthe licensed BCG. Our goal was to identify new vaccine benchmarks by identifying immune responses that distinguish individuals able to eradicate theinfection (TB-resisters) from individuals with latent infection (LTBI-participants). TB-resisters had higher frequencies of circulating CD8+ glucose monomycolate (GMM)+ Granzyme-B+ Tcells than LTBI-participants and higher proportions of polyfunctional conventional and nonconventional Tcells expressing Granzyme-B and/or PD-1 after exvivo M. tuberculosis stimulation of blood mononuclear cells. LTBI-participants had higher expression of activation markers and cytokines, including IL10, and IFNγ. An exploratory analysis of BCG-recipients with minimal exposure to TB showed absence of CD8+GMM+Granzyme-B+ Tcells, lower or equal proportions of Granzyme-B+PD-1+ polyfunctional Tcells than TB-resisters and higher or equal than LTBI-participants. In conclusion, highGranzyme-B+PD-1+ Tcell responses to M.tuberculosis and, possibly, of CD8+GMM+Granzyme-B+ Tcells may be desirable for new TB vaccines.