Migratory and lymphoid-resident dendritic cells cooperate to efficiently prime naive CD4 T cells.
ABSTRACT To initiate an adaptive immune response, rare antigen-specific naive CD4(+) T cells must interact with equally rare dendritic cells (DCs) bearing cognate peptide-major histocompatibility complex (MHC) complexes. Lymph nodes (LNs) draining the site of antigen entry are populated by lymphoid-resident DCs as well as DCs that have immigrated from tissues, although the requirement for each population in initiating the T cell response remains unclear. Here, we show that antigen processing and presentation by both lymphoid-resident and migratory DCs was required for clonal selection and expansion of CD4(+) T cells after subcutaneous immunization. Early antigen presentation by lymphoid-resident DCs initiated activation and trapping of antigen-specific T cells in the draining LN, without sufficing for clonal expansion. Migratory DCs, however, interacted with the CD4(+) T cells retained in the LN to induce proliferation. Therefore, distinct DC subsets cooperate to alert and trap the appropriate cell and then license its expansion and differentiation.
Article: Dendritic cell subtypes in mouse lymphoid organs: cross-correlation of surface markers, changes with incubation, and differences among thymus, spleen, and lymph nodes.[show abstract] [hide abstract]
ABSTRACT: Freshly isolated, mature dendritic cells (DC) from mouse lymphoid organs were analyzed by immunofluorescent labeling and flow cytometry to determine the number of discrete subpopulations and to assess possible lineage markers. The permanence of surface markers was then determined by overnight culture of the DC. Three DC subtypes were discerned, CD8alpha- DEC-205-, CD8alpha+ DEC-205+, and CD8alpha- DEC-205+, with different tissue distributions. The majority of DC expressed high levels of class II MHC, expressed CD11c, and expressed the costimulator molecules CD80, CD86, and CD40; CD80 and CD40 were further up-regulated on culture. DC also expressed low levels of L-selectin that were up-regulated on culture. Thymus contained predominantly CD8alpha+ DEC205+ CD11b- DC, resembling a major subpopulation of DC in other tissues but unique in expressing BP-1. Spleen contained predominantly two DC populations in equal proportions: one CD8alpha+ DEC-205+ CD11b- as in the thymus, and the other CD8alpha- DEC-205- CD11b+. Lymph nodes contained the same two DC populations as in spleen, but in addition a third population of CD8alpha- DEC-205+ CD11b- DC. The CD8alpha expression of splenic DC subpopulations did not change on culture. Although DEC-205 was up-regulated on culture so all DC became positive, the difference in the level between subpopulations was maintained. However, CD11b was up-regulated on culture, so all subpopulations became positive and finally expressed equivalent levels. Some aspects of this complex, but discrete, pattern of surface marker expression can be correlated with differences in lineage origin and functional activity of the DC.The Journal of Immunology 08/1997; 159(2):565-73. · 5.79 Impact Factor
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ABSTRACT: Dendritic cells (DC) are a heterogeneous cell population that bridge the innate and adaptive immune systems. CD8alpha DC play a prominent, and sometimes exclusive, role in driving amplification of CD8(+) T cells during a viral infection. Whether this reliance on a single subset of DC also applies for CD4(+) T cell activation is unknown. We used a direct ex vivo antigen presentation assay to probe the capacity of flow cytometrically purified DC populations to drive amplification of CD4(+) and CD8(+) T cells following infection with influenza virus by different routes. This study examined the contributions of non-CD8alpha DC populations in the amplification of CD8(+) and CD4(+) T cells in cutaneous and systemic influenza viral infections. We confirmed that in vivo, effective immune responses for CD8(+) T cells are dominated by presentation of antigen by CD8alpha DC but can involve non-CD8alpha DC. In contrast, CD4(+) T cell responses relied more heavily on the contributions of dermal DC migrating from peripheral lymphoid tissues following cutaneous infection, and CD4 DC in the spleen after systemic infection. CD4(+) T cell priming by DC subsets that is dependent upon the route of administration raises the possibility that vaccination approaches could be tailored to prime helper T cell immunity.PLoS ONE 02/2008; 3(2):e1691. · 4.09 Impact Factor