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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4575-4581.
Prepublished online as a Blood First Edition Paper on February 1, 2007; DOI 10.1182/blood-2006-07-029090.
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Submitted July 26, 2006
Accepted January 6, 2007
Long-term T cell reconstitution after haematopoietic stem cell transplantation in primary T cell immunodeficient patients is associated with myeloid chimerism and possibly the primary disease phenotype
M. Cavazzana-Calvo, F. Carlier, F. Le Deist, E. Morillon, P. Taupin, D. Gautier, I. Radford-Weiss, S. Caillat-Zucman, B. Neven, S. Blanche, R. Cheynier, A. Fischer, and S. Hacein-Bey-Abina*
INSERM U768, Universite Rene Descartes-Paris, Hopital Necker-Enfants Malades, Paris, France
Departement de Biotherapies, AP-HP, Hopital Necker-Enfants Malades, Paris, France
Centre d'Etude des Deficits Immunitaires, Hopital Necker- Enfants Malades, Paris, France
Departement de Biostatistique, Hopital Necker- Enfants Malades, Paris, France
Unite des Virus Lents, Institut Pasteur, Paris, France
Laboratoire de cytogenetique, Hopital Necker- Enfants Malades, Paris, France
Laboratoire d'Immunologie, Hopital Necker- Enfants Malades, Paris, France
Unite d'Immunologie et Hematologie Pediatrique, Hopital Necker- Enfants Malades, Paris, France
* Corresponding author; email: salima.hacein-bey{at}nck.ap-hop-paris.fr.
We studied T cell reconstitution in 31 primary T cell immunodeficient patients who had undergone haematopoietic stem cell transplantation (HSCT) over 10 years previously. In 19 patients, there was no evidence of myeloid chimerism because little or no myeloablation had been performed. Given this context, we sought factors associated with good, long-term T cell reconstitution. We found that all patients having undergone full myeloablation had donor myeloid cells and persistent thymopoiesis, as evidenced by the presence of naive T cells carrying T cell receptor excision circles (TRECs). In nine patients with host myeloid chimerism, sustained thymic output was also observed and appeared to be associated with c deficiency. It is therefore possible that the complete absence of thymic progenitors characterizing this condition created a more favourable environment for thymic seeding by a population of early progenitor cells with the potential for self-renewal, thus enabling long-term (> 10 years) T cell production.

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