Immunoregulatory and lipid presentation pathways are upregulated in human face transplant rejection

Abstract

METHODS.Using skin biopsies prospectively collected over 9 years from 7 face transplant patients, we studied rejection by gene expression profiling, histology, immunostaining, and T cell receptor sequencing. RESULTS. Grade 1 rejection did not differ significantly from nonrejection, suggesting that it does not represent a pathologic state. In grade 2, there was a balanced upregulation of both proinflammatory T cell activation pathways and antiinflammatory checkpoint and immunomodulatory pathways, with a net result of no tissue injury. In grade 3, IFN-γ-driven inflammation, antigen-presenting cell activation, and infiltration of the skin by proliferative T cells bearing markers of antigen-specific activation and cytotoxicity tipped the balance toward tissue injury. Rejection of VCAs and solid organ transplants had both distinct and common features. VCA rejection was uniquely associated with upregulation of immunoregulatory genes, including SOCS1; induction of lipid antigen-presenting CD1 proteins; and infiltration by T cells predicted to recognize CD1b and CD1c. CONCLUSION.Our findings suggest that the distinct features of VCA rejection reflect the unique immunobiology of skin and that enhancing cutaneous immunoregulatory networks may be a useful strategy in combatting rejection. TRIAL REGISTRATION. ClinicalTrials.gov NCT01281267.

Tissue adaptation and clonal segregation of human memory T cells in barrier sites

“…For example, skin T cells can manifest as a T H 17 response in cutaneous candidiasis 43 and psoriasis 44 , consistent with a T RM -mediated response. Conversely, T H 1 and cytotoxic responses are associated with rejection of facial transplants 45 , suggesting potential infiltration from circulation. In the lung, where T RM cells are T H 1-like or regulatory, an overactive T H 2 response promotes allergic airway disease 46 , suggesting functional alterations of T RM , as shown in mouse studies 47 .…”

Cellular activation pathways and interaction networks in vascularized composite allotransplantation

“…Additionally, it has been demonstrated that both donor and recipient-derived immune cells may contribute to the development of allograft rejection ( 12 ). Given the recognition of CD8 + effector T cells as the main (but not only) protagonists of VCA allograft rejection, this cell type is predominantly targeted by current clinical immunosuppression regimens (Tacrolimus, Steroids, mycophenolate mofetil (MMF)) ( 13 ). To further improve our understanding of VCA pathoimmunology, there is a critical need to review the current understanding of how different cell types contribute to VCA rejection ( Supplementary Figure 1 ).…”

Functionalizing multi-component bioink with platelet-rich plasma for customized in-situ bilayer bioprinting for wound healing

“…Generally speaking, there would be an immune response after transplantation, which is most distinct in the inflammatory phase of wound repair, which is manifested locally by the infiltration of immune cells and the release of inflammatory cytokines [ 64 ]. Whether the inflammatory response at this stage is stable and controllable plays a vital role in the development of wound into regeneration or prolonged inflammation.…”