However, other studies have challenged this position and explored various hypotheses for the differential rejection of tissues, including differences in the mode of immune presentation between primarily vascularized transplants and conventional skin grafts, which experience a prolonged period of ischemia and a non-specific inflammatory response that provides a hostile milieu for presentation of alloantigen.ĭespite some findings to the contrary in animal models, and reports of acute rejection targeted to other tissues including mucosa and muscle (unpublished data) in the absence of clinically detectable skin rejection, the literature is broadly supportive of skin as a common target of acute rejection in both experimental and clinical settings. Indeed, Murray’s early work at the interface of transplantation and reconstructive surgery solidified the immunological preeminence of skin in the hierarchy of tissues. The skin has historically been recognized as highly immunogenic.
#SKIN DEEP OXFORD AL UPDATE#
The aim of this review is to provide an update on skin immunology in the context of VCA rejection, monitoring of transplant health and to identify outstanding questions pertinent to an improved understanding of this unique and visible transplant component. Indeed, there is increasing interest in exploring the use of sentinel flaps to provide an immunological window for monitoring of solid organ transplants. While the potential for false negatives (where the skin appears rejection-free, but another tissue is affected) is recognized (albeit poorly defined), clinical observation of skin is utilized as a core component of monitoring in all VCAs with an exposed skin component.
However, none of these hypotheses has uniform support in the literature, and in recent years, there has been increasing appreciation of the skin as an immune organ in its own right, housing a complex network of immune cells and processes. The aggressive immune responses against skin have variously been attributed to the mode of transplantation (typically as skin grafts, which undergo secondary revascularization following a period of ischemia), the presence of putative skin-specific antigens, and the role of skin as a barrier organ, containing numerous immunologically active cells and extracellular components. The primary site of VCA acute rejection is most often the skin, which is highly immunogenic and susceptible to recipient immune responses, compared to other VCA tissues (historically skin transplantation has been used as a rigorous challenge for immunosuppressive or transplant tolerance protocols ). When compared to solid organ transplantation (SOT), VCA recipients can expect to experience a higher incidence of acute rejection, with approximately 85% experiencing one or more episodes during their first post-transplant year. This applies for highly selected cases where conventional, autologous techniques are insufficient to meet such reconstructive requirements. Vascularized composite allotransplantation (VCA) has become an established option for the restoration of form and function following complex injury or when specialized functional tissues are devitalized. This review focuses on the immunology of skin, skin rejection in vascularized composite allografts, and the recent advances in monitoring the health of transplanted tissues using distant “sentinel” flaps. Early clinical studies show sentinel flap rejection to correlate well with facial VCA skin rejection, and abdominal wall rejection demonstrates concordance with visceral rejection, but further studies are required.
Skin-resident T REG cells proliferate in response to inflammation and contribute to long-term VCA survival in small animal models. Recent Findingsĭiscrete populations of T memory cells provide distributed immune protection in skin, and cycle between skin, lymph nodes, and blood. The purpose of this review is to provide relevant background to the role of skin in vascularized transplantation medicine. Using transplanted skin as a monitor can provide a powerful tool for surveillance of rejection in a transplant. Skin provides a window into the health of an individual.
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