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

There is great need for vaccines against tuberculosis (TB) more efficacious than the licensed BCG. Our goal was to identify new vaccine benchmarks by identifying immune responses that distinguish individuals able to eradicate the infection (TB-resisters) from individuals with latent infection (LTBI-partici-pants). TB-resisters had higher frequencies of circulating CD8+ glucose monomy-colate (GMM)+ Granzyme-B+ T cells than LTBI-participants and higher propor-tions of polyfunctional conventional and nonconventional T cells expressing Granzyme-B and/or PD-1 after ex vivo M. tuberculosis stimulation of blood mono-nuclear cells. LTBI-participants had higher expression of activation markers and cytokines, including IL10, and IFNg. An exploratory analysis of BCG-recipients with minimal exposure to TB showed absence of CD8+GMM+Granzyme-B+ T cells, lower or equal proportions of Granzyme-B+PD-1+ polyfunctional T cells than TB-resisters and higher or equal than LTBI-participants. In conclusion, high Granzyme-B+PD-1+ T cell responses to M. tuberculosis and, possibly, of CD8+GMM+Granzyme-B+ T cells may be desirable for new TB vaccines.