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ctt-journal > Schlegel et al. (Abstract)

Schlegel et al. (Abstract)

Cellular Therapy and Transplantation (CTT), Vol. 3, No. 12
doi: 10.3205/ctt-2011-No12-abstract53

© The Authors. This abstract is provided under the following license: Creative Commons Attribution 3.0 Unported

Abstract accepted for "5th Raisa Gorbacheva Memorial Meeting Hematopoietic Stem Cell Transplantation in Children and Adults", Saint Petersburg, Russia, September 18–20, 2011

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Prospective analysis of immune reconstitution in pediatric stem cell transplant recipients in the HLA-identical setting and across HLA-barriers — lessons learnt?

Paul G. Schlegel, Matthias Wölfl, Matthias Eyrich

University Children’s Hospital, Wuerzburg, Germany

Correspondence: Prof. Dr. Paul G. Schlegel, University Children's Hospital Wuerzburg, Josef-Schneider-Str.2, D-97080 Würzburg, Germany, E-mail: schlegel@spam is badmail.uni-wuerzburg.de

Abstract

After a first wave of peripheral T cell expansion, regenerating naive T-cells emerge 3 to 6 months after allogeneic stem cell transplantation. We characterized regenerating naive T-cells after CD34 selected peripheral blood stem cell transplantation (in the HLA-identical setting) using a multimodal approach of immunophenotyping, measurement of cytokine productivity, CDR3-size spectratyping and analysis of the T-cell receptor excision circle (TREC) content. After being completely absent in the first weeks after transplant, naive T-cells (CD45RA+ for CD4, and CD27+CD45RA+ for CD8) emerged after 3 months and continuously increased thereafter. In parallel with the increase in naive T-cells, the number of CD62L+ and CD28+ T-cells increased. The rate of homeostatic proliferation, assessed by the intracellular expression of the nuclear antigen Ki67, peaked in CD4+ and CD8+ naive T-cells before day 180 and decreased to baseline levels thereafter. Interleukin-2 production of peripheral mononuclear cells after stimulation with PMA & Ionomycin increased when naive T-cells exceeded15% of peripheral T-cells. Interestingly, both CD4+ and CD8+ naive T-cells expressed a completely normal T-cell receptor (TCR) repertoire diversity and thereby contributed to correction of an initially skewed repertoire complexity. The increase of naive T-cells in the peripheral blood was paralleled by an increase of TREC+ T-cells, indicating that these T-cells were de novo generated in the thymus. Analysis of thymic function using the TREC-assay revealed that lack of GvHD, a higher transplanted CD34 stem cell number and transplantation because of a nonmalignant disease was associated with enhanced thymic production of naive T-cells. In the HLA-non-identical setting (haploidentical transplantation), the time to T-cell recovery is dependent on the mode of graft processing (CD34 selection vs. CD3/CD19 depletion vs. novel approaches).

In summary, naive T-cells contribute significantly to overcome the state of T-cell deficiency in the early phase post-transplant by introducing a diverse TCR repertoire, shortening the lymphopenic period by homeostatic proliferation, and producing cytokines essential for T-cell activation and survival. Improvement of T-cell reconstitution after allogeneic stem cell transplantation in the near future will basically depend on new strategies aimed at enhancing thymic production of naive T-cells.

Citation: Cellular Therapy and Transplantation, St. Petersburg

Keywords: allogeneic stem cell transplantation, CD34 selection, immune reconstitution, T-cells