Our aim was to look at whether the only available vaccine against tuberculosis (TB), BCG, stimulates the immune system to make as so-called “regulatory CD4+ T cells”, or “Tregs.” These white blood cells are very important for controlling the immune system after a vaccination. This means the cells make sure that the vaccine does not cause too much, or too little, immunity. The latter immunity, in turn, has to protect the vaccinated person against the disease for which he/she is vaccinated.
We tested blood from 10 week-old infants, routinely vaccinated with BCG at birth, and showed that 3 distinct types of Tregs form after vaccination. These 3 types of Tregs differ in how they control immunity. We believe that protection against childhood tuberculosis, afforded by newborn vaccination with BCG, involves a dynamic balance between immunity that protects against TB, and Tregs. We further propose that all 3 Treg populations should be measured when testing in the lab whether a TB vaccine will work or not.
To assess whether vaccination of human newborns with BCG (Bacille Calmette Guerin) induces regulatory CD4+ T cells (Tregs), we incubated whole blood of 10 week-old infants, routinely vaccinated at birth, with BCG for 12 hours. We showed that 3 distinct Treg subsets are induced: Interleukin (IL)-10-expressing T-regulatory type 1 (Tr1) cells, transforming growth factor (TGF)-β-expressing T-helper type 3 (Th3) cells, and Foxp3-expressing, presumedly naturally occuring Tregs, or nTregs. IL-10 and TGF-β expression occurred only in specific cells that do not express conventional effector (type 1) cytokines; co-expression of Foxp3+ and type 1 cytokines did rarely occur in the same cells. Depletion of CD127lowCD25high nTregs resulted in modest, but consistent, increases in proliferation induced by purified protein derivative; however, effects of neutralization of TGF-β or IL-10 on proliferation were variable and inconsistent. We hypothesize that protection against childhood tuberculosis afforded by newborn vaccination with BCG will involve a dynamic balance between conventional effector immunity and regulatory CD4+ T cell (Treg) immunity. We further propose that all 3 regulatory CD4+ T cell populations should be assessed in immunogenicity studies of TB vaccines.