TY  - JOUR
A1  - Dücker, Ruth Pia
A1  - Baer, Patrick C.
A1  - Bücker, Aileen
A1  - Hünecke, Sabine
A1  - Pfeffermann, Lisa-Marie
A1  - Modlich, Ute
A1  - Bakhtiar, Shahrzad
A1  - Bader, Peter
A1  - Zielen, Stefan
A1  - Schubert, Ralf
T1  - Hematopoietic stem cell transplantation restores naïve t-cell populations in atm-deficient mice and in preemptively treated patients with ataxia-telangiectasia
T2  - Frontiers in immunology
N2  - Background: Ataxia-telangiectasia (A-T) is a multisystem disorder with progressive cerebellar ataxia, immunodeficiency, chromosomal instability, and increased cancer susceptibility. Cellular immunodeficiency is based on naïve CD4+ and CD8+ T-cell lymphopenia. Hematopoietic stem cell transplantation (HSCT) offers a potential to cure immunodeficiency and cancer due to restoration of the lymphopoietic system. The aim of this investigation was to analyze the effect of HSCT on naïve CD4+ as well as CD8+ T-cell numbers in A-T.
Methods: We analyzed total numbers of peripheral naïve (CD45RA+CD62L+) and memory (CD45RO+CD62L−) CD4+ and CD8+ T-cells of 32 A-T patients. Naïve (CD62LhighCD44low) and memory (CD62LlowCD44high) T-cells were also measured in Atm-deficient mice before and after HSCT with GFP-expressing bone marrow derived hematopoietic stem cells. In addition, we analyzed T-cells in the peripheral blood of two A-T patients after HLA-identic allogeneic HSCT.
Results: Like in humans, naïve CD4+ as well as naïve CD8+ lymphocytes were decreased in Atm-deficient mice. HSCT significantly inhibited thymic lymphomas and increased survival time in these animals. Donor cell chimerism increased up to more than 50% 6 months after HSCT accompanied by a significant increase of naïve CD4 and CD8 T-cell subpopulations, but not of memory T-cells. This finding was also identified in the blood of the A-T patients after HSCT.
Conclusion: HSCT seems to be a feasible strategy to overcome immunodeficiency and might be a conceivable strategy to avoid T-cell driven cancer in A-T at higher risk for malignancy. Naïve CD4 and CD8 T-cells counts are suitable markers for monitoring immune reconstitution post-HSCT. However, risks and benefits of HSCT in A-T have to be properly weighted.
KW  - ataxia telangiectasia
KW  - stem cell transplantation
KW  - ATM
KW  - immune deficiency
KW  - CD45RA naïve lymphocytes
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/51806
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-518061
SN  - 1664-3224
N1  - Copyright © 2019 Duecker, Baer, Buecker, Huenecke, Pfeffermann, Modlich, Bakhtiar, Bader, Zielen and Schubert. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
VL  - 10
IS  - Art. 2785
SP  - 1
EP  - 10
PB  - Frontiers Media
CY  - Lausanne
ER  -