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Publication : NK cell patrolling and elimination of donor-derived dendritic cells favor indirect alloreactivity.

First Author  Garrod KR Year  2010
Journal  J Immunol Volume  184
Issue  5 Pages  2329-36
PubMed ID  20139277 Mgi Jnum  J:159639
Mgi Id  MGI:4452189 Doi  10.4049/jimmunol.0902748
Citation  Garrod KR, et al. (2010) NK cell patrolling and elimination of donor-derived dendritic cells favor indirect alloreactivity. J Immunol 184(5):2329-36
abstractText  Direct presentation of foreign MHC molecules expressed by donor-derived dendritic cells (DCs) has generally been considered the dominant pathway of allorecognition in acute transplant rejection. However, recent studies implicate preferential activation of the indirect pathway by host DCs. The respective importance of each pathway and the mechanisms that determine their relative contributions remain to be clearly established. In this study, using two-photon microscopy, we visualized host NK cell interactions with syngeneic and allogeneic DCs within intact lymph nodes of mice. Upon contact with allogeneic DCs, NK cells formed prolonged interactions that led directly to target cell lysis. This rapid elimination limited the ability of allogeneic DCs to stimulate primary and recall T cell responses. To discriminate whether donor or host DCs are principally involved in presenting Ag derived from allografts, we used CD11c-diphtheria toxoid receptor mice to conditionally ablate CD11c(+) DCs and to show that direct presentation by donor DCs is alone insufficient to elicit acute allograft rejection. We thus propose that rapid elimination of allogeneic DCs limits direct Ag presentation and thereby favors the indirect pathway of alloreactivity.
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