title: Evaluation of the expression and function of the P2X7 receptor and ART1 in human regulatory T-cell subsets.
abstract: Regulatory T cells that express CD39 (CD39+ Treg) exhibit specific immunomodulatory properties. Ectonucleotidase CD39 hydrolyses ATP and ADP. ATP is a ligand of the P2X7 receptor and induces the shedding of CD62L and apoptosis. However, the role of ATP in CD39+ Treg cells has not been defined. Furthermore, NAD can activate the P2X7 receptor via ADP-ribosyltransferase (ART) enzymes and cause cell depletion in murine models. We evaluated the expression and function of P2X7 and ART1 in CD39+ Treg and CD39- Treg cells in the presence or absence of ATP and NAD. We isolated peripheral blood mononuclear cells from healthy subjects and purified CD4+ T cells, CD4+ CD25+ T cells and CD4+ CD25+ CD39+ T cells. P2X7 and ART1 expression was assessed by flow cytometry and real-time PCR. Our results showed low P2X7 expression on CD39+ Treg cells and higher levels of ART1 expression in CD4+ CD39+ T cells than the other subtypes studied. Neither shedding of CD62L nor cell death of CD39+ Treg or CD39- Treg cells was observed by 1mM ATP or 60μM NAD. In contrast, P2Xs receptor-dependent proliferation with 300μM ATP, was inhibited by NAD in the different cell types analysed. The NAD proliferation-inhibition was increased with P2Xs and A2a agonist and was reversed with P2Xs and A2a antagonist, therefore NAD inhibits P2Xs-dependent proliferation and A2a activation. In conclusion, our results suggest that the altered function and expression of P2X7 and ART1 in the human CD39+ Treg or CD39- Treg cells could participate in the resistance against cell death induced by ATP or NAD.
authors: Laboratory of Immunology and Cellular and Molecular Biology, Faculty of Chemical Sciences, UASLP, San Luis Potosí, S.L.P., Mexicohttp://10.10.23.110:8080/TDXPSLIVELATEX/gateway/elsevierjournal/index.jsp#
authors: Juan D
authors: JD
authors: Cortés-Garcia
authors: Division of Molecular Biology, Instituto Potosino de Investigación Científica y Tecnológica, San Luis Potosí, S.L.P. Mexico.
authors: Cintya
authors: C
authors: López-López
authors: Laboratory of Immunology and Cellular and Molecular Biology, Faculty of Chemical Sciences, UASLP, San Luis Potosí, S.L.P., Mexicohttp://10.10.23.110:8080/TDXPSLIVELATEX/gateway/elsevierjournal/index.jsp#
authors: Nancy
authors: N
authors: Cortez-Espinosa
authors: Unit of Medicine Investigation IMSS, Zacatecas, Zac, Mexico.
authors: Mariana H
authors: MH
authors: García-Hernández
authors: Laboratory of Immunology and Cellular and Molecular Biology, Faculty of Chemical Sciences, UASLP, San Luis Potosí, S.L.P., Mexicohttp://10.10.23.110:8080/TDXPSLIVELATEX/gateway/elsevierjournal/index.jsp#
authors: Juan M
authors: JM
authors: Guzmán-Flores
authors: Department of Immunology, Faculty of Medicine, UASLP, San Luis Potosí, S.L.P. Mexico.
authors: Esther
authors: E
authors: Layseca-Espinosa
authors: Laboratory of Immunology and Cellular and Molecular Biology, Faculty of Chemical Sciences, UASLP, San Luis Potosí, S.L.P., Mexicohttp://10.10.23.110:8080/TDXPSLIVELATEX/gateway/elsevierjournal/index.jsp#
authors: Liliana
authors: L
authors: Portales-Cervantes
authors: Laboratory of Immunology and Cellular and Molecular Biology, Faculty of Chemical Sciences, UASLP, San Luis Potosí, S.L.P., Mexicohttp://10.10.23.110:8080/TDXPSLIVELATEX/gateway/elsevierjournal/index.jsp#. Electronic address: dportale@uaslp.mx.
authors: Diana P
authors: DP
authors: Portales-Pérez
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics / Q000276:immunology*; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001081:Apyrase / Q000235:genetics / Q000276:immunology; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D016130:Immunophenotyping; D019041:L-Selectin / Q000235:genetics / Q000276:immunology; D008297:Male; D009243:NAD / Q000494:pharmacology*; D010627:Phenethylamines / Q000494:pharmacology; D061251:Primary Cell Culture; D043683:Receptors, Adenosine A2 / Q000235:genetics / Q000276:immunology; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
chemical_list: D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D015703:Antigens, CD; D058851:GPI-Linked Proteins; C546468:P2RX7 protein, human; D010627:Phenethylamines; D043683:Receptors, Adenosine A2; D058486:Receptors, Purinergic P2X7; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; D009243:NAD; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D019041:L-Selectin; D000255:Adenosine Triphosphate; D036002:ADP Ribose Transferases; C449301:ART1 protein, human; D001081:Apyrase; C067869:CD39 antigen; D000241:Adenosine
keywords: ART1; ATP; CD39; Immune regulation; NAD; P2X7 receptor