Original Article

Leukemia (2008) 22, 344–352; doi:10.1038/sj.leu.2405041; published online 22 November 2007

Involvement of mature donor T cells in the NK cell reconstitution after haploidentical hematopoietic stem-cell transplantation

S Nguyen1,2, M Kuentz3, J-P Vernant2, N Dhedin2, D Bories4, P Debré1 and V Vieillard1

  1. 1Laboratoire d'Immunologie Cellulaire et Tissulaire, Institut National de la Santé et de la Recherche Médicale (INSERM) U543, Hôpital Pitié-Salpêtrière, Paris, France
  2. 2Service d'Hématologie Clinique, Hôpital Pitié-Salpêtrière, Paris, France
  3. 3Service d'Hématologie Clinique, Hôpital Henri Mondor, Créteil, France
  4. 4Service d'Hématologie, Hôpital Henri Mondor, Créteil, France

Correspondence: Dr V Vieillard, Laboratoire d'Immunologie Cellulaire et Tissulaire, Institut National de la Santé et de la Recherche Médicale (INSERM) U543, Hôpital Pitié-Salpêtrière, Paris, France. E-mail: vincent.vieillard@chups.jussieu.fr

Received 3 May 2007; Revised 9 October 2007; Accepted 22 October 2007; Published online 22 November 2007.

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Abstract

We previously demonstrated that natural killer (NK) cells generated after haploidentical stem-cell transplantation (SCT) are blocked at an immature state characterized by phenotypic features and impaired functioning and that this may affect transplantation outcome. We hypothesize that the absence of mature donor T cells in the graft may affect NK cell differentiation. NK cells from 21 transplant recipients who underwent either partial (pTCD; n=11) or extensive (eTCD; n=10) T-cell depletion were compared with NK cells from their healthy donors. We report that despite the strong graft-versus-host disease (GvHD) reaction, pTCD patients, with T cells present during SCT, had a better clinical outcome than patients with eTCD transplants. In addition, the frequency of CD3-CD56bright and NKG2A+ NK cells was much lower in pTCD than in eTCD patients after transplantation, and the level of cytotoxicity against primary haplo-mismatched blasts was significantly more pronounced after pTCD than eTCD transplants. These finding strongly suggest that mature donor T cells in the graft may play a key role in NK cell differentiation in vivo, after haploidentical SCT.

Keywords:

NK cells, haploidentical stem-cell transplantation, mature T cells, NKG2A, cytotoxicity

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