A question of persistence: Langerhans cells and graft-versus-host disease.
Bottom Line: Langerhans cells (LCs) have been scrutinized many times in studies of the pathogenesis of graft-versus-host disease (GVHD).As migratory dendritic cells, LCs are capable of direct antigen presentation to cytotoxic T cells.In this issue of Experimental Dermatology, a new study examines at the relationship between recipient LCs and chronic GVHD.
Affiliation: Human Dendritic Cell Laboratory, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.Show MeSH
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Mentions: Human studies had previously shown that LCs were in cell cycle (6) and understanding the turnover of LCs, especially after reduced intensity transplantation, became a pivotal question. Several studies asked whether persistent recipient LCs were associated with an increased risk of acute GVHD and might therefore offer a new target of therapeutic intervention (7,8). However, a key factor was overlooked, namely that acute GVHD itself may cause sufficient cutaneous inflammation to deliver a knockout blow to resident LCs, resulting in the recruitment of donor-derived cells (5). This presented a paradox: the very ‘risk factor’ for GVHD, a high proportion of persistent recipient LCs, is more likely to be observed in the absence of GVHD. Another way to consider this is that recipient LCs, although self-renewing, are actually self-limiting in terms of priming donor T cells: the more inflammation that results, the more likely they are to disappear (Fig. 1).
Affiliation: Human Dendritic Cell Laboratory, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.