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A question of persistence: Langerhans cells and graft-versus-host disease.

Collin M, Jardine L - Exp. Dermatol. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Human Dendritic Cell Laboratory, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

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Related in: MedlinePlus

Association of GVHD with donor LC engraftment. LCs are self-renewing in the steady state. Conditioning with chemo/radiotherapy for HSCT leads to transient depletion and repopulation, probably by local proliferation. Inflammation caused by acute GVHD leads to loss of recipient LCs and engraftment of donor cells (also self-renewing). This means that a biopsy taken after acute GVHD is likely to find an inverse association between the persistence of recipient LCs and acute GVHD. Owing to the fact that acute GVHD is the most significant risk factor for chronic GVHD, high donor LC engraftment at 100 days is also more likely to be associated with chronic GVHD, although this has not been tested. Conversely, patients without acute GVHD are more likely to retain recipient LCs. Whether the level of recipient LCs remaining predicts the incidence of chronic GVHD is the question posed by Adani and colleagues in Experimental Dermatology. *Other reports suggest 90% engraftment may occur even in the absence of GVHD.
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fig01: Association of GVHD with donor LC engraftment. LCs are self-renewing in the steady state. Conditioning with chemo/radiotherapy for HSCT leads to transient depletion and repopulation, probably by local proliferation. Inflammation caused by acute GVHD leads to loss of recipient LCs and engraftment of donor cells (also self-renewing). This means that a biopsy taken after acute GVHD is likely to find an inverse association between the persistence of recipient LCs and acute GVHD. Owing to the fact that acute GVHD is the most significant risk factor for chronic GVHD, high donor LC engraftment at 100 days is also more likely to be associated with chronic GVHD, although this has not been tested. Conversely, patients without acute GVHD are more likely to retain recipient LCs. Whether the level of recipient LCs remaining predicts the incidence of chronic GVHD is the question posed by Adani and colleagues in Experimental Dermatology. *Other reports suggest 90% engraftment may occur even in the absence of GVHD.

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).


A question of persistence: Langerhans cells and graft-versus-host disease.

Collin M, Jardine L - Exp. Dermatol. (2014)

Association of GVHD with donor LC engraftment. LCs are self-renewing in the steady state. Conditioning with chemo/radiotherapy for HSCT leads to transient depletion and repopulation, probably by local proliferation. Inflammation caused by acute GVHD leads to loss of recipient LCs and engraftment of donor cells (also self-renewing). This means that a biopsy taken after acute GVHD is likely to find an inverse association between the persistence of recipient LCs and acute GVHD. Owing to the fact that acute GVHD is the most significant risk factor for chronic GVHD, high donor LC engraftment at 100 days is also more likely to be associated with chronic GVHD, although this has not been tested. Conversely, patients without acute GVHD are more likely to retain recipient LCs. Whether the level of recipient LCs remaining predicts the incidence of chronic GVHD is the question posed by Adani and colleagues in Experimental Dermatology. *Other reports suggest 90% engraftment may occur even in the absence of GVHD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150527&req=5

fig01: Association of GVHD with donor LC engraftment. LCs are self-renewing in the steady state. Conditioning with chemo/radiotherapy for HSCT leads to transient depletion and repopulation, probably by local proliferation. Inflammation caused by acute GVHD leads to loss of recipient LCs and engraftment of donor cells (also self-renewing). This means that a biopsy taken after acute GVHD is likely to find an inverse association between the persistence of recipient LCs and acute GVHD. Owing to the fact that acute GVHD is the most significant risk factor for chronic GVHD, high donor LC engraftment at 100 days is also more likely to be associated with chronic GVHD, although this has not been tested. Conversely, patients without acute GVHD are more likely to retain recipient LCs. Whether the level of recipient LCs remaining predicts the incidence of chronic GVHD is the question posed by Adani and colleagues in Experimental Dermatology. *Other reports suggest 90% engraftment may occur even in the absence of GVHD.
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).

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.

View Article: PubMed Central - PubMed

Affiliation: Human Dendritic Cell Laboratory, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Show MeSH
Related in: MedlinePlus