Intrathymic progenitor cell transplantation across histocompatibility barriers results in the persistence of early thymic progenitors and T-cell differentiation

9Citations
Citations of this article
21Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Donor hematopoietic stem cells (HSCs) can correct T-cell deficiencies in patients with severe combined immunodeficiency by replacing resident thymus cells. However, as those progenitors that naturally migrate to the thymus are not capable of supporting long-term thymopoiesis, a successful transplant is thought to require the ongoing migration of donor progenitors. We previously showed that the forced intrathymic administration of histocompatible HSCs can sustain long-term thymopoiesis in ZAP-70immunodeficient mice. However, it is not known whether T-cell reconstitution across histocompatibility barriers is modulated by intrathymic vs intravenous administration of HSCs. In the absence of conditioning, long-term thymopoiesis by semiallogeneic progenitors was detected in mice transplanted via the intrathymic, but not the intravenous, route. In intrathymic-transplanted mice, ongoing thymopoiesis was associated with a 10-fold higher level of early thymic progenitors (ETPs). The enhanced reconstitution capacity of these intrathymic-derived ETPs was corroborated by their significantly augmented myeloid lineage potential compared with endogenous ETPs. Notably, though, myeloablative conditioning resulted in a reduced expansion of intrathymic-administered donor ETPs. Thus, in the absence of conditioning, the forced thymic entry of HSCs results in a sustained T-cell development across histocompatibility barriers, highlighting the capacity of the thymus to support cells with long-term renewal potential.

Cite

CITATION STYLE

APA

De Barros, S. C., Vicente, R., Chebli, K., Jacquet, C., Zimmermann, V. S., & Taylor, N. (2013). Intrathymic progenitor cell transplantation across histocompatibility barriers results in the persistence of early thymic progenitors and T-cell differentiation. Blood, 121(11), 2144–2153. https://doi.org/10.1182/blood-2012-08-447417

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free