Unconventional, adenosine-producing suppressor T cells induced by dendritic cells exposed to BPZE1 pertussis vaccine. Issue 4 (18th June 2015)

• Record Type: Journal Article
• Authors: Fedele, Giorgio; Sanseverino, Isabella; D'Agostino, Krizia; Schiavoni, Ilaria; Locht, Camille; Horenstein, Alberto L; Malavasi, Fabio; Ausiello, Clara M
• Is Part Of: Journal of leukocyte biology. Volume 98:Issue 4(2015)
• Page Start: 631
• Page End: 639
• Publication Date: 2015-06-18
• Subjects: ectoenzymes -- regulatory T cells -- nucleotides; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.3A0315-101R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : T-lymphocytes activated by BPZE1-DC shift to suppressor stage through expression of ectoenzyme networks able to convert extracellular nucleotides into adenosine. 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.