Hematopoietic Stem Cell Transplantation Restores Naïve T-Cell Populations in Atm -Deficient Mice and in Preemptively Treated Patients With Ataxia-Telangiectasia
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...
Gespeichert in:
Veröffentlicht in: | Frontiers in immunology 2019-11, Vol.10, p.2785-2785 |
---|---|
Hauptverfasser: | , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | 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.
We analyzed total numbers of peripheral naïve (CD45RA
CD62L
) and memory (CD45RO
CD62L
) CD4
and CD8
T-cells of 32 A-T patients. Naïve (CD62L
CD44
) and memory (CD62L
CD44
) 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.
Like in humans, naïve CD4
as well as naïve CD8
lymphocytes were decreased in
-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.
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. |
---|---|
ISSN: | 1664-3224 1664-3224 |
DOI: | 10.3389/fimmu.2019.02785 |