Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells.
Whereas naive T cells migrate only to secondary lymphoid organs, activation by antigen confers to T cells the ability to home to non-lymphoid sites. Activated effector/memory T cells migrate preferentially to tissues that are connected to the secondary lymphoid organs where antigen was first encountered. Thus, oral antigens induce effector/memory cells that express essential receptors for intestinal homing, namely the integrin alpha4beta7 and CCR9, the receptor for the gut-associated chemokine TECK/CCL25 (refs 6, 8, 9). Here we show that this imprinting of gut tropism is mediated by dendritic cells from Peyer's patches. Stimulation of CD8-expressing T cells by dendritic cells from Peyer's patches, peripheral lymph nodes and spleen induced equivalent activation markers and effector activity in T cells, but only Peyer's patch dendritic cells induced high levels of alpha4beta7, responsiveness to TECK and the ability to home to the small intestine. These findings establish that Peyer's patch dendritic cells imprint gut-homing specificity on T cells, and thus license effector/memory cells to access anatomical sites most likely to contain their cognate antigen.
Mora
J Rodrigo
JR
The Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Bono
Maria Rosa
MR
Manjunath
N
N
Weninger
Wolfgang
W
Cavanagh
Lois L
LL
Rosemblatt
Mario
M
Von Andrian
Ulrich H
UH
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D007156:Immunologic Memory; D016023:Integrins / Q000378:metabolism; D007421:Intestine, Small / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008545:Melanoma; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009928:Organ Specificity; D010581:Peyer's Patches / Q000276:immunology*; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing; D013154:Spleen / Q000276:immunology; D014407:Tumor Cells, Cultured
C119309:CC chemokine receptor 9; C491541:Ccl25 protein, mouse; D019742:Chemokines, CC; D016023:Integrins; D054388:Receptors, CCR; D019707:Receptors, Chemokine; D016201:Receptors, Lymphocyte Homing; C071777:integrin alpha4beta7