title: Reconstitution of T-cell compartment after in utero stem cell transplantation: analysis of T-cell repertoire and thymic output.
abstract: OBJECTIVE
  In utero transplantation of hematopoietic stem cells allows immune reconstitution of fetuses with severe combined immunodeficiency. The objective of this work was to study the quality of T-cell reconstitution following this procedure.
  
  
  METHODS
  We evaluated the kinetics and extent of T-cell reconstitution in five infants with severe combined immune deficiency (SCID), three with a B+ and two with a B- phenotype, who received haploidentical stem cell transplantation before birth. To this end, we measured the frequency of T-cell receptor excision circles (TREC) and the diversity of the T-cell repertoire.
  
  
  RESULTS
  In utero transplantation led to engraftment of donor-derived T lymphocytes which attained normal numbers in four infants, who are in good health. In the three patients with a B+ phenotype, generation of a heterogeneous T-cell repertoire was associated with development of TREC levels comparable to those of SCID patients treated by post-natal transplantation and of healthy babies. Of the two patients with a B- phenotype, one developed mixed T-cell chimerism and a substantial number of circulating T cells, associated with a variable heterogeneity of the T-cell repertoire; TREC levels were normal soon after birth, but declined thereafter. The remaining B- patient remained lymphopenic with a skewed T-cell repertoire and very low TREC levels. This patient eventually required transplantation from a matched unrelated donor at 5 years of age, but died of EBV-related lymphoproliferative disease.
  
  
  CONCLUSIONS
  These data indicate that in utero transplantation of fetuses with B+ SCID allows generation of newly diversified T lymphocytes and ensures long-term reconstitution of cell-mediated immunity.
authors.affiliation: Terzo Servizio Analisi, Spedali Civili of Brescia and Department of Chemistry, University of Brescia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pirovano
authors.forename: Luigi Daniele
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: Fabio
authors.initials: F
authors.lastname: Malacarne
authors.forename: Evelina
authors.initials: E
authors.lastname: Mazzolari
authors.forename: Fulvio
authors.initials: F
authors.lastname: Porta
authors.forename: Arnalda
authors.initials: A
authors.lastname: Lanfranchi
authors.forename: Silvia
authors.initials: S
authors.lastname: Giliani
authors.forename: Sandro
authors.initials: S
authors.lastname: Zucca
authors.forename: Sergio
authors.initials: S
authors.lastname: Pecorelli
authors.forename: Alberto
authors.initials: A
authors.lastname: Albertini
authors.forename: Alberto G
authors.initials: AG
authors.lastname: Ugazio
authors.forename: Luisa
authors.initials: L
authors.lastname: Imberti
mesh_terms: D000328:Adult; D005260:Female; D046128:Fetal Therapies; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007107:Immune System / Q000502:physiology; D007223:Infant; D011247:Pregnancy; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D012038:Regeneration; D016511:Severe Combined Immunodeficiency / Q000628:therapy; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000502:physiology
chemical_list: D011948:Receptors, Antigen, T-Cell