Differential Intrasplenic Migration of Dendritic Cell Subsets Tailors Adaptive Immunity

• CD4+ and CD8+ T cells preferentially occupy separate areas of the splenic T cell zone
• DC-intrinsic CCR7 is required for migration within the spleen after i.v. immunization
• 33D1+ and XCR1+ DCs migrate into CD4+ and CD8+ T cell areas, respectively
• Loss of DC subset and T-cell-lineage pairing abrogates either CD4+ or CD8+ T cell immunity

SummaryEvidence suggests that distinct splenic dendritic cell (DC) subsets activate either CD4+ or CD8+ T cells in vivo. This bias has been partially ascribed to differential antigen presentation; however, all DC subsets can activate both T cell lineages in vitro. Therefore, we tested whether the organization of DC and T cell subsets in the spleen dictated this preference. We discovered that CD4+ and CD8+ T cells segregated within splenic T cell zones prior to immunization. After intravenous immunization, the two major conventional DC populations, distinguished by 33D1 and XCR1 staining, migrated into separate regions of the T cell zone: 33D1+ DCs migrated into the CD4+ T cell area, whereas XCR1+ DCs migrated into the CD8+ T cell area. Thus, the post-immunization location of each DC subset correlated with the T cell lineage it preferentially primes. Preventing this co-localization selectively impaired either CD4+ or CD8+ T cell immunity to blood-borne antigens.

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