Significance of selectively targeted apoptotic rete cells in graft-versus-host disease

Considerable data exist regarding the mechanisms of allostimulation and homing (the effector phases) in graft-versus-host disease (GVHD). Current dogma suggests that target specificity involves preferential injury to epithelial surfaces of the skin and squamous mucosae, liver, and gut. Little attention has been devoted, however, to mechanisms of cellular targeting or to whether heterogeneity exists in target tissues with regard to a threshold for cellular injury. A recent breakthrough in understanding the target stage of GVHD indicates that the predominant pathway of injury to squamous epithelial cells involves apoptosis. Moreover, apoptotic injury may be associated or unassociated with local T-cell infiltration and involves phenotypically and antigenically distinctive epithelial cells within the basal layer of the skin and squamous mucosa. These cells are confined to rete ridges in the skin and retelike prominences in the dorsal tongue and are designated as selectively targeted apoptotic rete (STAR) cells. The discovery of STAR cells in GVHD paves the way for speculation and experimentation to determine why these subpopulations are selectively vulnerable and how soluble and cellular effectors of apoptosis contribute to their ultimate demise. Novel approaches to GVHD treatment derived from understanding mechanisms of selective epithelial injury are likely to use strategies to render target cells less susceptible to the apoptosis that is ultimately responsible for organ dysfunction and failure. (C) 2004 American Society for Blood and Marrow Transplantation.