Reconstitution of T-cell compartment after in utero stem cell transplantation: Analysis of T-cell repertoire and thymic output

Silvia Pirovano, Luigi Daniele Notarangelo, Fabio Malacarne, Evelina Mazzolari, Fulvio Porta, Arnalda Lanfranchi, Silvia Giliani, Sandro Zucca, Sergio Pecorelli, Alberto Albertini, Alberto G. Ugazio, Luisa Imberti

Research output: Contribution to journalArticle

Abstract

Background and Objectives. 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. Design and 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. Interpretation and 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.

Original languageEnglish
Pages (from-to)450-461
Number of pages12
JournalHaematologica
Volume89
Issue number4
Publication statusPublished - Apr 2004

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Keywords

  • In utero stem cell transplantation
  • Severe combined immunodeficiency
  • T-cell repertoire
  • TREC

ASJC Scopus subject areas

  • Hematology

Cite this

Pirovano, S., Notarangelo, L. D., Malacarne, F., Mazzolari, E., Porta, F., Lanfranchi, A., Giliani, S., Zucca, S., Pecorelli, S., Albertini, A., Ugazio, A. G., & Imberti, L. (2004). Reconstitution of T-cell compartment after in utero stem cell transplantation: Analysis of T-cell repertoire and thymic output. Haematologica, 89(4), 450-461.