101. In vivo Treg expansion by TNFRSF25 stimulation inhibits allergic lung inflammation (97.11)
- Author
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Matthew Tsai, Taylor Schreiber, Dietlinde Wolf, Jackeline Chirinos, Louis Gonzalez, Robert Levy, and Eckhard Podack
- Subjects
Immunology ,Immunology and Allergy - Abstract
TNF receptor super family member 25 (TNFR25, DR3) is constitutively and highly expressed by CD4+FoxP3+ regulatory T cells (Treg). Here we have utilized a TNFR25 agonistic monoclonal antibody, 4C12, to study the effects of TNFR25 signaling on Treg in vivo. We have previously demonstrated that signaling through TNFR25, in the absence of TCR signals, induces rapid and selective expansion of natural Treg in vivo to 30-35% of all CD4+ T cells within 4 days. TNFR25-expanded Treg remained highly suppressive ex vivo. Here we demonstrate that although certain IL-2 antibody complexes expand Treg to a similar degree, only in vivo TNFR25-expanded Treg are protective against allergic lung inflammation, a model for asthma, by reversing the T-effector to T-regulatory ratio in the lung, suppressing IL-13 and Th2 cytokine production and blocking eosinophil exudation into bronchio-alveolar fluid. Unlike TNFR25 responses by T effector cells, which require TCR engagement, expansion of Treg by TNFR25 signaling is not dependent upon stimulation by exogenous antigens. Our studies define a novel mechanism for Treg control and important functions for TNFR25/TL1A in regulating auto aggression that balance its known role in enhancing auto immunity.
- Published
- 2010
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