Commentary
Isabelle Magalhaes, Raija K
Abstract
Non-human primate models aid to design novel vaccine strategies. We analyzed therefore the dynamics of cellular immune responses induced by a bacille Calmette-Guérin (BCG) / recombinant BCG (rBCG, perfringolysin plus Ag85A/B, TB10.4) prime, subsequent adenoviral (Ad35 expressing Ag85A/B and TB10.4) boosts followed by a challenge with M. tuberculosis (Mtb, Erdman strain) in peripheral blood mononuclear cells from rhesus macaques. T-cell compartment mobilization was defined by CD45RA/CCR7/CD27/CD28 expression on CD4+, CD8αα+ and CD8αβ+ T-cells and functional analysis (STAT-5 phosphorylation) was carried out using multicolor flow cytometry. CD4+ as well as CD8+ T-cells showed a marked decrease in IL-7 receptor alpha-chain (IL-7Rα) expression in vaccinated animals (n=12/12) after the first adenoviral boost, but not in control animals (who received saline). BCG- and rBCG- vaccinated animals showed a dramatic decrease of precursor (CD45RA+CCR7+) and subsequent increase of activated central memory (CD45RA-CCR7+) T-cells in the CD4+, CD8αα+ and CD8αβ+ T-cell compartments 2 weeks after Mtb challenge. In contrast, this pattern was observed in control animals only 7 weeks after Mtb challenge. Expression of IL-7Rα was markedly reduced in CD4+ T-cell subsets two weeks after Mtb challenge in BCG-vaccinated animals, yet not in rBCG-vaccinated animals or control animals. These data show that vaccination profoundly shapes the dynamics of immune memory T-cells associated with Mtb infection.