Date: Tuesday, May 5, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Background: Injury and repair processes are highly controlled, common occurrences of healthy tissue remodeling. During this process, cellular antigens that are not normally exposed to the network of surrounding immune cells are detected and presented to T cells to begin a controlled inflammatory response including the production of IL22 from Th17-CD4 T cells, culminating in the repair of perturbed epithelial membranes. We have termed the transient expression and sequestration of these cellular self-antigens during tissue injury and repair, the SALSAA (Self Antigens Left Sequestered After Activation) cycle. Amongst the 20 potential SALSAAs we have screened, only Collagen type V/XI (ColV), k-α-1 tubulin (kα1T) and vimentin elicit reproducible cellular immune responses in our human and non-human primate cohorts. In addition, all three proteins have a strong association with chronic rejection of lung (kα1T, ColV) and heart (vimentin, ColV) transplants and with related pathologies such as cardiovascular disease and IPF (ColV). We have previously shown, using the tvDTH assay, that depletion of CD39+ T cells from normal healthy individuals uncovers a population of CD4 effector T cells that specifically respond to select SALSAAs (ColV, kα1T and vimentin) in a Th17 dependent manner. Hypothesis: We hypothesize that natural T cell responses to ColV, kα1T and vimentin, originating in fetal life, consist of Th17-like effectors producing the pro-inflammatory cytokines IL17 and TNFα along with epithelial cell-protective IL-22. Results: Using intra-cellular cytokine staining, we found that removal of CD39+ T cells from PBMCs of normal, healthy individuals uncovers a population of CD4 effector T cells that produce IL17, TNFα and IL22 in response to overnight stimulation with ColV, kα1T and vimentin but not to Col-I. This natural, Th17 memory response in normal individuals closely parallels the footpad swelling response in the 24 hour tvDTH assay. Conclusions: Consistent with our hypothesis, the cytoprotective cytokine IL22 was a significant part of the natural T memory response to ColV, kα1T, and vimentin. We propose that the Th17 response we observe in chronically rejecting transplant patients will exhibit little to no IL22 production from CD4 effector T cells leading to an imbalance between inflammatory IL17 and pro-repair IL22 production.
To cite this abstract in AMA style:Sullivan J, Wilkes D, Mohanakumar T, Burlingham W. Characterization of Natural T Effector Memory Cells Specific for Collagen type V, k-α-1-Tubulin and Vimentin [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/characterization-of-natural-t-effector-memory-cells-specific-for-collagen-type-v-k-1-tubulin-and-vimentin/. Accessed April 20, 2021.
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