Decreased Thymic Output Contributes to Immune Defects in Septic Patients
Authors: Steffen Noack
Norbert Weissmann
Konstantin Mayer
Andreas Hecker
Gregor Bein
Matthias Hecker
Natascha Sommer
Werner Seeger
Holger Hackstein
Journal: Journal of Clinical Medicine (2020)
Discipline: CLINICAL MEDICINE
Keywords: inflammation; lymphopenia; sepsis; thymus.
Affiliations: Excellence Cluster Cardio-Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University of Giessen, 35392 Giessen, Germany., Department of General and Thoracic Surgery, Justus-Liebig-University of Giessen, 35392 Giessen, Germany., Department of Transfusion Medicine and Hemostaseology, University Hospital Erlangen, 91054 Erlangen, Germany., Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig-University, 35392 Giessen, Germany., Department of Pulmonary and Sleep Medicine, ViDia Hospitals, 76137 Karlsruhe, Germany.

Abstract:  Background: Prolonged immunosuppression and hypoinflammation, termed compensatory anti-inflammatory response syndrome (CARS), contribute to high morbidity and mortality in the late phase of sepsis. Although apoptosis is a well-known cause of lymphopenia in sepsis, the contribution of thymic output to immune alterations in sepsis and potential compensatory mechanisms are largely unknown. Methods: We investigate the release of CD4+ T cells from the thymus and their peripheral proliferation by evaluating T-cell receptor excision circles (TREC) and the expression of CD31 as markers for recent thymic emigrants (RTE) and their proliferative offspring in septic patients with relevant lymphopenia in the CARS phase. Moreover, we determine the aging of T cells by measuring telomere characteristics. Results: In septic patients, we found decreased CD4+ T-helper cell numbers, while CD8+ T cell numbers were unchanged. As a possible cause, we detected increased apoptosis of CD4+ T-helper cells and decreased levels of IL-7, which promotes the maturation of T cells in the thymus. Accordingly, the relative number of mature CD4+ T cells, TREC-containing CD4+ T cells, and CD31+ RTEs (characteristic of thymic output) was decreased, while the relative number of CD31-T cells (peripherally expanded naïve T cells) was increased. Furthermore, the telomere length decreased, although telomerase activity and markers for the shelterin complex were increased specifically in CD4+ but not in CD8+ T cells. Conclusion: We thus conclude that, in addition to T-cell apoptosis, decreased thymic output and increased aging of CD4+ T cells may contribute to lymphopenia and immunosuppression in sepsis. Increased proliferation of peripheral T cells cannot compensate for these effects. 

Retracted: No

PubPeer comments:
 Figure 1D: The apoptosis protein protein array for CD8 T cells from Control and Sepsis look 100% identical in every spot. Please check. ![file] , 
 After contrast enhancement it looks to me like Control and Sepsis are the same blot. Maybe the authors could check and in case it is a duplication, try to arrange a correction...if that is possible in JCM. ![file] , 
 We thank for the comment. Unfortunately, the  Control blot is shown twice and the  Sepsis blot is missing. We previously asked the journal to correct the mistake and sent the correct figure. Unfortunately, it was not updated, yet. We apologize for the mistake and the time delay in correction. We will approach JCM again to correct the figure. , 
 #3 Your effort to correct this is highly appreciated. Then my conclusion would be that  Journal of Clinical Medicine seems either incapable or unwilling of correcting their own manuscripts within a reasonable timeframe, both is bad. , 
 **CORRECTION** * In the original article, there were errors in Figure 1D (panel CD8-Control) [1]. Changes are below. The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. The original article has been updated. * https: www.mdpi.com 2077-0383 11 15 4497 htm ,