Publication Date:
2014-12-06
Description:
Promising results from murine models and early stage clinical trials have shown that adoptive transfer of regulatory T cells (Treg) prevents graft-versus-host disease (GvHD). However, the primary target of Treg mediated protection against GvHD is yet to be fully defined. We have previously shown that the presence of Treg during effector T cell priming is able to ameliorate cutaneous GvH reactions in vitro by blocking effector cell migration. This has led to the hypothesis that Treg modulation of dendritic cells (DC) could be a key mechanism by which Treg exert their protective role in GvHD. DC are fundamental for the initiation of allo-reactive immune responses and are critical in GvHD pathogenesis. We investigated the effect of Treg on the phenotypic profile and allo-reactive functions of DCs. Furthermore, the impact of Treg treatment on the ability of DCs to induce GvH target tissue damage was examined for the first time using an in vitro human GvHD skin explant model. Immature, mature and Treg treated DCs were generated from immuno-magnetic isolated monocytes (im-DC, mat-DC and Treg-DC respectively). The three moDC populations were generated using the well-established 6 day culture with GM-CSF and IL-4 followed by 24 hour LPS maturation. Treg were added on day 3 of moDC culture. Im-DC, mat-DC and Treg-DC were harvested on day 7 and tested in parallel as stated below. Prior to functional assays Treg-moDC were isolated by FACS sorting via FSC/SSC/CD3neg gating to remove Treg present in the co-culture. Our results revealed that Treg-DC displayed a semi-mature phenotype with CD83, CD80 and CD86 expression significantly lower than mat-moDC (p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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