The Journal of Experimental Medicine
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Published online 17 April 2000.
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© The Rockefeller University Press, 0022-1007/2000/4/1381/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 8, April 17, 2000 1381-1394


Original Article

Localization of Distinct Peyer's Patch Dendritic Cell Subsets and Their Recruitment by Chemokines Macrophage Inflammatory Protein (Mip)-3{alpha}, Mip-3β, and Secondary Lymphoid Organ Chemokine

Akiko Iwasakia and Brian L. Kelsalla

a Immune Cell Interaction Unit, Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1890
Immune Cell Interaction Unit, Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1890.301-402-2240301-496-7473

bkelsall{at}nih.gov

We describe the anatomical localization of three distinct dendritic cell (DC) subsets in the murine Peyer's patch (PP) and explore the role of chemokines in their recruitment. By two-color in situ immunofluorescence, CD11b+ myeloid DCs were determined to be present in the subepithelial dome (SED) region, whereas CD8{alpha}+ lymphoid DCs are present in the T cell–rich interfollicular region (IFR). DCs that lack expression of CD8{alpha} or CD11b (double negative) are present in both the SED and IFR. By in situ hybridization, macrophage inflammatory protein (MIP)-3{alpha} mRNA was dramatically expressed only by the follicle-associated epithelium overlying the SED, while its receptor, CCR6, was concentrated in the SED. In contrast, CCR7 was expressed predominantly in the IFR. Consistent with these findings, reverse transcriptase polymerase chain reaction analysis and in vitro chemotaxis assays using freshly isolated DCs revealed that CCR6 was functionally expressed only by DC subsets present in the SED, while all subsets expressed functional CCR7. Moreover, none of the splenic DC subsets migrated toward MIP-3{alpha}. These data support a distinct role for MIP-3{alpha}/CCR6 in recruitment of CD11b+ DCs toward the mucosal surfaces and for MIP-3β/CCR7 in attraction of CD8{alpha}+ DCs to the T cell regions. Finally, we demonstrated that all DC subsets expressed an immature phenotype when freshly isolated and maintained expression of subset markers upon maturation in vitro. In contrast, CCR7 expression by myeloid PP DCs was enhanced with maturation in vitro. In addition, this subset disappeared from the SED and appeared in the IFR after microbial stimulation in vivo, suggesting that immature myeloid SED DCs capture antigens and migrate to IFR to initiate T cell responses after mucosal microbial infections.

Key Words: chemokine • migration • T cell region • mucosal immunity • follicle-associated epithelium


Abbreviations used in this paper: DC, dendritic cell; DN, double-negative; FAE, follicle-associated epithelium; HRP, horseradish peroxidase; IFR, interfollicular region; ISH, in situ hybridization; MIP, macrophage inflammatory protein; PP, Peyer's patch; SED, subepithelial dome; SLC, secondary lymphoid organ chemokine.

© 2000 The Rockefeller University Press


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