title: Mixed chimerism evolution is associated with T regulatory type 1 (Tr1) cells in a β-thalassemic patient after haploidentical haematopoietic stem cell transplantation.
abstract: In a cohort of β-Thalassemia (β-Thal) transplanted with haploidentical-HSCT we identified one transplanted patient characterized by persistent mixed chimerism (PMC) for several months after HSCT. In this unique β-Thal patient we assessed the donor engraftment overtime after transplantation, the potential loss of the non-shared HLA haplotype, and the presence of CD49b(+)LAG-3(+) T regulatory type 1 (Tr1) cells, previously demonstrated to be associated with PMC after HLA-related HSCT for β-Thal. The majority of the patient's erythrocytes were of donor origin, whereas T cells were initially mostly derived from the recipient, no HLA loss, but an increased frequency of circulating Tr1 cells were observed. For the first time, we showed that when the proportion of residual donor cells decreases, the frequency of CD49b(+)LAG-3(+) Tr1 cells declines, reaching the levels present in healthy subjects. These findings confirm previous results obtained in transplant related settings for β-Thal, and supported the central role of Tr1 cells in promoting and maintaining PMC after allo-HSCT.
authors.affiliation: a Laboratory of Immunogenetics and Transplant Biology; IME Foundation at Polyclinic of Tor Vergata ; Rome , Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Andreani
authors.affiliation: b San Raffaele Telethon Institute for Gene Therapy (TIGET); Division of Regenerative Medicine; Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute ; Milan , Italy.
authors.forename: Monica Emma
authors.initials: ME
authors.lastname: Gianolini
authors.affiliation: a Laboratory of Immunogenetics and Transplant Biology; IME Foundation at Polyclinic of Tor Vergata ; Rome , Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Testi
authors.affiliation: a Laboratory of Immunogenetics and Transplant Biology; IME Foundation at Polyclinic of Tor Vergata ; Rome , Italy.
authors.forename: MariaRosa
authors.initials: M
authors.lastname: Battarra
authors.affiliation: a Laboratory of Immunogenetics and Transplant Biology; IME Foundation at Polyclinic of Tor Vergata ; Rome , Italy.
authors.forename: Galluccio
authors.initials: G
authors.lastname: Tiziana
authors.affiliation: a Laboratory of Immunogenetics and Transplant Biology; IME Foundation at Polyclinic of Tor Vergata ; Rome , Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Morrone
authors.affiliation: c International Center for Transplantation in Thalassemia and Sickle Cell Anemia-Mediterranean Institute of Hematology; Policlinic of the University of Rome Tor Vergata ; Rome , Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Sodani
authors.affiliation: c International Center for Transplantation in Thalassemia and Sickle Cell Anemia-Mediterranean Institute of Hematology; Policlinic of the University of Rome Tor Vergata ; Rome , Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Lucarelli
authors.affiliation: b San Raffaele Telethon Institute for Gene Therapy (TIGET); Division of Regenerative Medicine; Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute ; Milan , Italy.|d Department of Pediatric Stem Cell Transplantation and Regenerative Medicine ; Stanford School of Medicine ; Stanford , CA USA.
authors.forename: Maria-Grazia
authors.initials: MG
authors.lastname: Roncarolo
authors.affiliation: b San Raffaele Telethon Institute for Gene Therapy (TIGET); Division of Regenerative Medicine; Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute ; Milan , Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Gregori
mesh_terms: D046528:Chimerism; D015331:Cohort Studies; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000378:metabolism; D017086:beta-Thalassemia / Q000235:genetics* / Q000628:therapy*
keywords: Haploidentical HSCT; T regulatory type 1 (Tr1) cells; mixed chimerism