Der Einfluss von T-Zell- und Dendritischen Zell-exprimiertem CD83 auf die Regulation von Immunantworten
Zusammenfassung der Projektergebnisse
CD83 was originally identified as marker for mature dendritic cells (DCs) and elevated CD83 expression has also been described for activated lymphocytes. In addition, we identified CD4+Foxp3+ regulatory T cells (Tregs) to express high levels of CD83. However, the physiological function of CD83 in different immune cell subsets remained elusive or is still discussed controversially. The aim of the present project was to gain further insights into the role of endogenous CD83 expression in CD11c+ DCs, CD4+Foxp3+ Tregs as well as CD4+Foxp3- conventional T cells. For this purpose, we have generated a new CD83flox mouse line (floxed exon 3, BALB/c background) and crossed it with the respective cre-expressing mouse lines to obtain cellspecific CD83-deficient mice. In accordance with a most recent publication (Wild et al., 2019), we could demonstrate that ablation of endogenous CD83 expression in DCs resulted in enhanced immune responses. In contrast, CD83 expression seems to be dispensable for the immune-suppressive function of CD4+Foxp3+ Tregs since we did not detect differences in the inhibitory capacity of CD83- deficient Tregs and Tregs isolated from control littermates. Recently, similar results have also been described by Doebbeler and colleagues who showed comparable suppressive capacity of Tregs from CD83flox/flox/Foxp3-cre mice compared to wildtype controls in vitro and in vivo (Doebbeler et al., 2018). Elevated CD83 has been demonstrated for activated CD4+ conventional T cells. In the present study we showed for the first time that endogenous CD83 expression orchestrate the activity of CD4+ conventional T cells. CD83-deficient T cells exhibited elevated proliferation and proinflammatory cytokine production in vitro. T cell-specific CD83-deficient mice developed severe contact hypersensitivity reaction. Moreover, ablation of endogenous CD83 expression resulted in aggravated T cell transfer colitis associated with enhanced IL-12 serum concentrations and increased expression of co-stimulatory molecules by CD11c+ DCs in diseased mice. Strikingly, in vitro co-culture experiments revealed that CD4+ T cell-expressed CD83 directly controls the activation of DCs by dampening IL-12 production and CD40 expression. Overall, our results clearly demonstrate that DC-derived and CD4+ conventional T cell-derived CD83 expression orchestrates inflammatory immune responses. Hence, inference with CD83 might represent a promising approach to improve immunity.
Projektbezogene Publikationen (Auswahl)
- (2016). CD83 expression has a CD4+ T cell-intrinsic inhibitory function in vitro and in vivo. 46th Annual Meeting of the German Society for Immunology, Hamburg, Germany
Watzstedt et al.
- (2017). T cell-specific CD83 deficiency correlates with increased CD4+ T cell activation. 47th Annual Meeting of the German Society for Immunology, Erlangen, Germany
Liedtke et al.
- (2018). Elevated activation of CD83-deficient CD4+ T cells. 5th European Congress of Immunology, Amsterdam, The Netherlands
Liedtke et al.
