Immunodeficiency: primary or acquired

Oral

Aging of Adaptive Immunity Driven by Chronic Antigen Exposition Has a Major Impact on the Course of Regenerative Processes Which Are Overlooked in Our Commonly Used Mouse Models

Thursday, June 15
5:45 PM - 7:00 PM

Antigen exposition over the life drives the adaptive immune system to an aged state characterized by a shift to effector-T cells (Teff). In contrast to naïve/central memory T cells, Teff can migrate to any inflamed site in the body and modify the intratissue inflammation. Recently, we could show that immune aging, defined by enhanced Teff levels, is associated with poorer outcome of a sterile bone fracture in trauma patients. Accumulation of those cells and release of inflammatory cytokines at the fracture hematoma blocks the osteoblast differentiation. In normal SPF mice, only few Teff are detectable and the impact on bone fracture healing is negligible. However, change of environmental housing conditions to non-SPF, induces an "aged" immune system within few weeks without signs of pathological infections. Remarkably, bone fracture healing is delayed compared to SPF animals and the level is related to the ratio between effector and regulatory T cells (Teff/Treg), as in patients. Consequently, depletion of CD8+ T-cells or adoptive transfer of Treg promote fracture healing if the ratio was successfully converted, supporting the causative role of adaptive immunity. Translating to other disease models, we confirmed the important impact of Teff/Treg on regenerative processes. Non-SPF but not SPF-mice develop NASH-like liver pathology under high-fat diet associated with accumulation of Teff in liver and fat. Teff also showed negative impact on muscle injury, transplantation, myocarditis. In summary, mice kept under well controlled non-SPF housing conditions and immune monitored are better disease models reflecting the impact of intratissue accumulation of Teff.




Hans-Dieter Volk

charite, inst.med.immunology and bcrt

Presentation(s):

    Send Email for Hans-Dieter Volk

    Simon Reinke

    bcrt, charite university medicine

    Presentation(s):

      Send Email for Simon Reinke

      Julia Kind

      bcrt & dept. endocrinology, charite university medicien berlin

      Presentation(s):

        Send Email for Julia Kind

        Sven Geissler

        bcrt/jwi, charite university medicine

        Presentation(s):

          Send Email for Sven Geissler

          Iuliia Kotko

          bcrt/imi, charite university medicine

          Presentation(s):

            Send Email for Iuliia Kotko

            Mathias Streitz

            bcrt/imi, charite university medicine

            Presentation(s):

              Send Email for Mathias Streitz

              Georg Duda

              bcrt/jwi, charite university medicine

              Presentation(s):

                Send Email for Georg Duda

                Joachim Spranger

                dept. endocrinology, charite university medicine berlin

                Presentation(s):

                  Send Email for Joachim Spranger

                  Katherina Schmidt-bleek

                  bcrt/jwi, charite university medicine

                  Presentation(s):

                    Send Email for Katherina Schmidt-bleek


                    Assets

                    Aging of Adaptive Immunity Driven by Chronic Antigen Exposition Has a Major Impact on the Course of Regenerative Processes Which Are Overlooked in Our Commonly Used Mouse Models



                    Attendees who have favorited this

                    Send Email for Aging of Adaptive Immunity Driven by Chronic Antigen Exposition Has a Major Impact on the Course of Regenerative Processes Which Are Overlooked in Our Commonly Used Mouse Models