On the relevance of TCR rearrangement circles as molecular markers for thymic output during experimental graft-versus-host disease.
Efficient reconstitution of the pool of peripheral T cells after hemopoietic stem cell transplantation (HSCT) is dependent on normal thymic function. However, the development of graft-vs-host disease (GVHD) in the context of allogeneic HSCT is associated with injurious effects on thymocyte development. In this study, we examined in models of syngeneic and allogeneic murine HSCT whether actual posttransplant thymic output is accurately reflected by analysis of signal-joint TCR rearrangement excision circles (sjTRECs). Our data demonstrate that the de novo generation of T cells following syngeneic HSCT of T cell-deficient B6.RAG2(-/-) (recombination-activating gene 2(-/-)) mice correlates firmly with an increase of sjTRECs in the thymus and spleen. However, the altered homeostasis of naive peripheral T cells in the presence of GVHD necessitates the combined analysis of cell division in vivo and determinations of sjTREC contents and total sjTREC numbers to draw informative conclusions. From our data, we substantiate that thymic output and peripheral division of newly generated T cells are diminished in the presence of acute GVHD in an experimental radiation/allogeneic HSCT model.
Krenger
Werner
W
Pediatric Immunology, Departments of Research and Clinical-Biological Sciences, University of Basel, and University Children's Hospital of Basel, Kantonsspital, Hebelstrasse 20, CH-4031 Basel, Switzerland. werner.krenger@unibas.ch
Schmidlin
Heike
H
Cavadini
Gionata
G
Holländer
Georg A
GA
D000208:Acute Disease; D000818:Animals; D002455:Cell Division; D004195:Disease Models, Animal; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D005819:Genetic Markers; D006086:Graft vs Host Disease / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D016130:Immunophenotyping; D051379:Mice; D008815:Mice, Inbred Strains; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology*; D014184:Transplantation, Homologous
D005819:Genetic Markers; D011948:Receptors, Antigen, T-Cell