gms | German Medical Science

44. Kongress der Deutschen Gesellschaft für Rheumatologie, 30. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie, 26. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie

31.08. - 03.09.2016, Frankfurt am Main

Thymic output after immunoablation and CD34-selected autologous stem cell transplantation generates a new and diverse pool of natural regulatory T cells in systemic lupus erythematosus

Meeting Abstract

  • Tobias Alexander - Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
  • Lars Templin - Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
  • Andreas Thiel - Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Berlin
  • Gerd-Rüdiger Burmester - Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
  • Renate Arnold - Charité - Universitätsmedzin Berlin, Hämatologie und Onkologie, Berlin
  • Falk Hiepe - Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. 44. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 30. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 26. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Frankfurt am Main, 31.08.-03.09.2016. Düsseldorf: German Medical Science GMS Publishing House; 2016. DocER.03

doi: 10.3205/16dgrh045, urn:nbn:de:0183-16dgrh0454

Veröffentlicht: 29. August 2016

© 2016 Alexander et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

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Background: Our previous research has provided the evidence that an autoreactive immune system can be “reset” into a healthy, tolerant state by immunoablative treatment to eradicate pathogenic effector cells, followed by transplantation of hematopoietic progenitor cells (HSCT). Here, we investigated the T cell reconstitution in 10 patients with refractory systemic lupus erythematosus (SLE) for up to 15 years after receiving immunoablation and ASCT.

Methods: Since 1998, 10 patients with refractory SLE received a CD34+-selected autologous stem cell transplantation after immunoablation with ATG and cyclophosphamide as part of a prospective monocentric phase I/II clinical trial. Their peripheral blood lymphocytes were investigated using multiparametric flow cytometry, including analysis of the TCR-Vbeta repertoire on CD4+ lymphocytes. Thymic activity was determined measuring absolute counts of peripheral blood CD31+ thymic naive Th cells. In addition, Tregs where analyzed for their expression of Helios, CD45RA and CD31. Healthy donors and patients after thymectomy for myasthenia gravis served as controls.

Results: In the first 6 months post-Tx most CD4+ T cells presented a CD45RO+ memory-like phenotype and TCR analysis revealed a highly restricted TCR Vbeta usage resulting from peripheral expansion. Subsequently, an increase in absolute numbers of CD31+ thymic naïve CD4+ T cells occurred 6-12 months post-Tx and persisted in significantly higher numbers compared to age-matched controls. Expression levels for Helios – a marker for natural Tregs – in recurring Tregs post-Tx was similar in SLE compared to healthy controls and thymectomized patients (~70%), but their coexpression levels for CD45RA and CD31 was significantly higher (26.4% vs. 20.6% vs. 7.1%). While expanded naturally occurring Helios+ Tregs in active SLE patients under conventional treatment showed a skewed TCR repertoire, the TCR repertoire of Tregs in responding patients after ASCT was diverse.

Conclusion: Our data show that immune reconstitution after ASCT is associated with a profound reconfiguration of the adaptive immune system, i.e. immune reset, characterized by stable thymic reactivation with recurrence and persistence of thymic naïve conventional and regulatory T cells. Thereby, thymic output generates a pool of new and diverse Helios+ Tregs after HSCT. Although Helios is regarded as a marker for naturally occurring Tregs, coexpression levels for CD31 and CD45RA better correlates with thymic output conditions for Tregs.