Unconventional, adenosine-producing suppressor T cells induced by dendritic cells exposed to BPZE1 pertussis vaccine

Abstract

BPZE1 is a live attenuated pertussis vaccine that successfully completed a phase 1 safety trial. This article describes the induction of unconventional suppressor T cells-producing ADO by MDDCs exposed to BPZE1 (BPZE1-DC) through distinct ectoenzymatic pathways that limit the damaging effect of inflammation. BPZE1-DC induces CD4(+) and CD8(+) T lymphocytes to express 2 sets of ectoenzymes generating ADO: 1 set is part of the conventional CD39/CD73 pathway, which uses ATP as substrate, whereas the other is part of the CD38/CD203a/CD73 pathway and metabolizes NAD(+). The contribution of the ADO-generating ectoenzymes in the regulatory response was shown by: 1) selective inhibition of the enzymatic activities of CD39, CD73, and CD38; 2) the ability of suppressor T cells to convert exogenously added ATP and NAD(+) to ADO; and 3) a positive correlation between ectoenzyme expression, ADO levels, and suppression abilities. Thus, T lymphocytes activated by BPZE1-DC shift to a suppressor stage, through the expression of ectoenzyme networks, and are able to convert extracellular nucleotides into ADO, which may explain the potent anti-inflammatory properties of BPZE1 observed in several murine models.