The Journal of Experimental Medicine
Fluorescence In Vivo Endomicroscopy
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Published online 10 January 2005 doi:10.1084/jem.20041645
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 2, 303-316
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ARTICLE

 Reciprocal and dynamic control of CD8 T cell homing by dendritic cells from skin- and gut-associated lymphoid tissues

J. Rodrigo Mora1,2, Guiying Cheng1,2, Dominic Picarella3, Michael Briskin3, Natasha Buchanan3, and Ulrich H. von Andrian1,2

1 The CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115
2 Department of Pathology, Harvard Medical School, Boston, MA 02115
3 Millennium Pharmaceuticals, Cambridge, MA 02139

CORRESPONDENCE Ulrich H. von Andrian: uva{at}cbr.med.harvard.edu

T cell activation by intestinal dendritic cells (DC) induces gut-tropism. We show that, reciprocally, DC from peripheral lymph nodes (PLN-DC) induce homing receptors promoting CD8 T cell accumulation in inflamed skin, particularly ligands for P- and E-selectin. Differential imprinting of tissue-tropism was independent of Th1/Th2 cytokines and not restricted to particular DC subsets. Fixed PLN-DC retained the capacity to induce selectin ligands on T cells, which was suppressed by addition of live intestinal DC. By contrast, fixed intestinal DC failed to promote gut-tropism and instead induced skin-homing receptors. Moreover, the induction of selectin ligands driven by antigen-pulsed PLN-DC could be suppressed "in trans" by adding live intestinal DC, but PLN-DC did not suppress gut-homing receptors induced by intestinal DC. Reactivation of tissue-committed memory cells modified their tissue-tropism according to the last activating DC's origin. Thus, CD8 T cells activated by DC acquire selectin ligands by default unless they encounter fixation-sensitive signal(s) for gut-tropism from intestinal DC. Memory T cells remain responsive to these signals, allowing for dynamic migratory reprogramming by skin- and gut-associated DC.

Abbreviations used: Ag, antigen; CFSE, carboxyfluorescein diacetate succinimidyl ester; FucT, fucosyltransferase; HI, homing index; IVM, intravital microscopy; MFI, mean fluorescence intensity; PLN, peripheral lymph nodes; PP, Peyer's patches; PSGL-1, P-selectin glycoprotein ligand-1.

The online version of this article contains supplemental material.


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