Efforts of the human immune system to maintain the peripheral CD8+ T cell compartment after childhood thymectomy

Manuela Zlamy; Giovanni Almanzar; Walther Parson; Christian Schmidt; Johannes Leierer; Birgit Weinberger; Verena Jeller; Karin Unsinn; Matthias Eyrich; Reinhard Würzner; Martina Prelog

doi:10.1186/s12979-016-0058-z

Efforts of the human immune system to maintain the peripheral CD8+ T cell compartment after childhood thymectomy

Immun Ageing. 2016 Feb 2:13:3. doi: 10.1186/s12979-016-0058-z. eCollection 2016.

Authors

Affiliations

¹ Department of Pediatrics, Medical University Innsbruck, Innsbruck, Austria.
² Department of Pediatrics, University Hospital Wuerzburg, University of Wuerzburg, Josef-Schneider-Str. 2, 97080 Wuerzburg, Germany.
³ Institute of Legal Medicine, Medical University Innsbruck, Innsbruck, Austria ; Penn State Eberly College of Science, University Park, PA USA.
⁴ Department of Haematology and Oncology, University of Greifswald, Greifswald, Germany.
⁵ Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria.
⁶ Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria.
⁷ Department of Radiology, Medical University Innsbruck, Innsbruck, Austria.
⁸ Department of Hygiene and Medical Microbiology, Medical University Innsbruck, Innsbruck, Austria.

Abstract

Background: Homeostatic mechanisms to maintain the T cell compartment diversity indicate an ongoing process of thymic activity and peripheral T cell renewal during human life. These processes are expected to be accelerated after childhood thymectomy and by the influence of cytomegalovirus (CMV) inducing a prematurely aged immune system. The study aimed to investigate proportional changes and replicative history of CD8+ T cells, of recent thymic emigrants (RTEs) and CD103+ T cells (mostly gut-experienced) and the role of Interleukin-(IL)-7 and IL-7 receptor (CD127)-expressing T cells in thymectomized patients compared to young and old healthy controls.

Results: Decreased proportions of naive and CD31 + CD8+ T cells were demonstrated after thymectomy, with higher proliferative activity of CD127-expressing T cells and significantly shorter relative telomere lengths (RTLs) and lower T cell receptor excision circles (TRECs). Increased circulating CD103+ T cells and a skewed T cell receptor (TCR) repertoire were found after thymectomy similar to elderly persons. Naive T cells were influenced by age at thymectomy and further decreased by CMV.

Conclusions: After childhood thymectomy, the immune system demonstrated constant efforts of the peripheral CD8+ T cell compartment to maintain homeostasis. Supposedly it tries to fill the void of RTEs by peripheral T cell proliferation, by at least partly IL-7-mediated mechanisms and by proportional increase of circulating CD103+ T cells, reminiscent of immune aging in elderly. Although other findings were less significant compared to healthy elderly, early thymectomy demonstrated immunological alterations of CD8+ T cells which mimic features of premature immunosenescence in humans.

Keywords: CD8; CMV; Naive T cells; TCR diversity; TRECs; Telomeres; Thymectomy.