Abstracts (complete list) - Wissenschaft Online

Fanny Edele, Rosalie Molenaar, Cindy Reinhold, Dominique Gütle, Jan C. Dudda, Reina
Mebius, Mathias Hornef, Stefan F. Martin
Environmental instruction of dendritic cells for T cell homing
receptor imprinting
Imprinting of tissue-specific homing receptors on T cells is induced by dendritic cells
(DC) in lymph nodes draining e.g. the skin or the small intestine. However, it is yet
unclear whether this process is governed by lymph node resident DC or rather by DC
immigrating from the peripheral tissue. Our recent demonstration that Langerhans cells
efficiently imprint skin homing receptors on T cells led us to the hypothesis that the
peripheral tissue microenvironment licenses dendritic cells for homing receptor
imprinting upon T cell priming in the draining lymph nodes. To analyse the role of nonhematopoietic
cells in the microenvironment of the skin and the small intestine in the
imprinting of the DC itself, we used co-cultures of bone marrow-derived (BM-) DC
pulsed with the T cell epitope GP33 from the LCMV glycoprotein, TCR transgenic P14
splenocytes and either dermal fibroblasts or small intestinal epithelial cells (SIEC). After
co-culture of peptide pulsed BM-DC, P14 cells and dermal fibroblasts we observed an upregulation
of the skin homing receptor E-selectin ligand on the CD8+ P14 T cells. In
contrast, in co-cultures with SIEC, we observed an up-regulation of the gut homing
receptors α4β7 integrin and CCR9 on the P14 T cells.
DC re-isolated from co-culture with SIEC had only marginally up-regulated CD103 (αE
integrin), but showed a clear expression of retinal dehydrogenases (RALDH). Thus, the
BM-DC had acquired features of gut-specific DC.
In summary, our results show that the peripheral tissue microenvironment induces
tissue-specific characteristics in DC and endows them with the capacity to imprint the
homing receptor profile specific for their tissue of origin on T cells in the draining lymph
nodes.