Immunodeficiency: primary or acquired

Oral Abstract Sessions

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
3:26 PM - 3:39 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.




Send Email for Hans-Dieter Volk

Send Email for Simon Reinke

Julia Kind

bcrt & dept. endocrinology, charite university medicien berlin

Presentation(s):

Send Email for Julia Kind

Send Email for Sven Geissler

Send Email for Iuliia Kotko

Send Email for Mathias Streitz

Send Email for Georg Duda

Joachim Spranger

dept. endocrinology, charite university medicine berlin

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Send Email for Joachim Spranger

Send Email for Katherina Schmidt-bleek


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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



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