title: TNF and regulatory T cells are critical for sepsis-induced suppression of T cells.
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.
authors.affiliation: Institute of Immunology University of Regensburg Regensburg Germany.
authors.forename: David
authors.initials: D
authors.lastname: Stieglitz
authors.affiliation: Institute of Immunology University of Regensburg Regensburg Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Schmid
authors.affiliation: Institute of Immunology University of Regensburg Regensburg Germany.
authors.forename: Nirav F
authors.initials: NF
authors.lastname: Chhabra
authors.affiliation: Institute of Immunology University of Regensburg Regensburg Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Echtenacher
authors.affiliation: Institute of Immunology University of Regensburg Regensburg Germany.
authors.forename: Daniela N
authors.initials: DN
authors.lastname: Männel
authors.affiliation: Institute of Immunology University of Regensburg Regensburg Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Mostböck
keywords: Immunosuppression; TNF receptors; Treg; suppressor cells