NDLI: Intrathymic administration of hematopoietic progenitor cells enhances T cell reconstitution in ZAP-70 severe combined immunodeficiency

Content Provider	PubMed Central
Author	Adjali, Oumeya Vicente, Rita R. Ferrand, Christophe Jacquet, Chantal Mongellaz, Cédric Tiberghien, Pierre Chebli, Karim Zimmermann, Valérie S. Taylor, Naomi
Copyright Year	2005
Abstract	Patients with severe combined immunodeficiency (SCID) present with opportunistic infections that are almost universally fatal in infancy. The mainstay treatment for these patients is allogeneic hematopoietic stem cell (HSC) transplantation, but sustained polyclonal T cell reconstitution is too often unsatisfactory. Although transplantation is conventionally performed by i.v. administration of HSC, we hypothesized that an intrathymic strategy would be superior. Indeed, several progenitor cell populations are incapable of homing to the thymus, the major site of T cell differentiation, and it appears that there are extensive time periods during which the thymus is refractory to progenitor cell import. To test this hypothesis, nonconditioned infant ZAP-70-deficient SCID mice were intrathymically injected with WT bone marrow progenitor cells, a procedure accomplished without surgical intervention. Upon intrathymic HSC injection, there was a more rapid T cell differentiation, with mature thymocytes detected by 4 weeks after transplantation. Intrathymic injection of HSC also resulted in significantly higher numbers of peripheral T cells, increased percentages of naïve T cells, and more diverse T cell receptor repertoires. Moreover, T cell reconstitution after intrathymic transplantation was obtained after injection of 10-fold fewer donor HSC. Thus, this intrathymic transplantation approach may improve the outcome of SCID patients by enhancing T cell reconstitution.
Related Links	http://dx.doi.org/10.1073/pnas.0504268102
Ending Page	13591
Page Count	6
Starting Page	13586
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	38
Volume Number	102
Language	English
Publisher	National Academy of Sciences
Publisher Date	2005-09-20
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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