TNF and regulatory T cells are critical for sepsis‐induced suppression of T cells

Immunity, Inflammation and Disease

David Stieglitz¹  Tobias Schmid¹  Nirav F. Chhabra¹  Bernd Echtenacher¹  Daniela N. Männel¹ 

[1] Institute of Immunology, University of Regensburg, Regensburg, Germany

关键词: Immunosuppression;    suppressor cells;    TNF receptors;    Treg;   

DOI  :  10.1002/iid3.75

来源: Wiley

【 摘 要 】

Abstract

The immune system in sepsis is impaired as seen by reduced numbers and function of immune cells and impaired antigen-specific antibody responses. We studied T cell function in septic mice using cecal ligation and puncture (CLP) as a clinically relevant mouse model for sepsis. The proliferative response of CD4⁺ and CD8⁺ T cells was suppressed in septic mice. Adoptive transfer experiments demonstrated that the T cells were not intrinsically altered by CLP. Instead, the septic host environment was responsible for this T cell suppression. While CLP-induced suppression was dependent on TNF activity, neither the activation of TNF receptors type 1 nor TNF receptor type 2 alone was sufficient to generate sepsis-induced suppression showing that the two TNF receptors can substitute each other. Specific depletion of regulatory T (Treg) cells improved the impaired T cell proliferation in septic recipients demonstrating participation of Treg in sepsis-induced suppression. In summary, sepsis leads to TNF-dependent suppression of T cell proliferation in vivo involving induction of Treg cells.

【 授权许可】

CC BY   
© 2015 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.