title: Batf3-independent langerin- CX3CR1- CD8α+ splenic DCs represent a precursor for classical cross-presenting CD8α+ DCs.
abstract: This study tests the hypothesis that CD8α(+) DCs in the spleen of mice contain an immature precursor for functionally mature, "classical" cross-presenting CD8α(+) DCs. The lymphoid tissues contain a network of phenotypically distinct DCs with unique roles in surveillance and immunity. Splenic CD8α(+) DCs have been shown to exhibit a heightened capacity for phagocytosis of cellular material, secretion of IL-12, and cross-priming of CD8(+) T cells. However, this population can be subdivided further on the basis of expression of both langerin/CD207 and CX(3)CR1. We therefore evaluated the functional capacities of these different subsets. The CX(3)CR1(+) CD8α(+) DC subset does not express langerin and does not exhibit the classical features above. The CX(3)CR1(-) CD8α(+) DC can be divided into langerin-positive and negative populations, both of which express DEC205, Clec9A, and high basal levels of CD86. However, the langerin(+) CX(3)CR1(-) CD8α(+) subset has a superior capacity for acquiring cellular material and producing IL-12 and is more susceptible to activation-induced cell death. Significantly, following purification and adoptive transfer into new hosts, the langerin(-) CX(3)CR1(-) CD8α(+) subset survives longer, up-regulates expression of langerin, and becomes more susceptible to activation-induced cell death. Last, in contrast to langerin(+) CX(3)CR1(-) CD8α(+), the langerin(-) CX(3)CR1(-) CD8α(+) are still present in Batf3(-/-) mice. We conclude that the classical attributes of CD8α(+) DC are confined primarily to the langerin(+) CX(3)CR1(-) CD8α(+) DC population and that the langerin(-) CX(3)CR1(-) subset represents a Batf3-independent precursor to this mature population.
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand; and tpetersen@malaghan.org.nz.
authors.forename: Troels R
authors.initials: TR
authors.lastname: Petersen
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand; and.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Knight
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand; and.
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Tang
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand; and School of Biological Sciences, Victoria University of Wellington, New Zealand.
authors.forename: Taryn L
authors.initials: TL
authors.lastname: Osmond
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand; and School of Biological Sciences, Victoria University of Wellington, New Zealand.
authors.forename: Ian F
authors.initials: IF
authors.lastname: Hermans
mesh_terms: D056704:Adaptive Immunity; D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D000943:Antigens, Differentiation / Q000032:analysis*; D000954:Antigens, Surface / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D050976:Basic-Leucine Zipper Transcription Factors / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D000073883:CX3C Chemokine Receptor 1; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D016922:Cellular Senescence; D003433:Crosses, Genetic; D003713:Dendritic Cells / Q000737:chemistry / Q000145:classification* / Q000276:immunology; D005260:Female; D005699:Galactosylceramides / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology; D016130:Immunophenotyping; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D037241:Mannose-Binding Lectins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010587:Phagocytosis / Q000276:immunology; D019707:Receptors, Chemokine / Q000032:analysis; D012097:Repressor Proteins / Q000032:analysis; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D000943:Antigens, Differentiation; D000954:Antigens, Surface; D050976:Basic-Leucine Zipper Transcription Factors; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D000073883:CX3C Chemokine Receptor 1; C498497:Cd207 protein, mouse; C471885:Cx3cr1 protein, mouse; D005699:Galactosylceramides; D015395:Histocompatibility Antigens Class I; D053762:Interleukin-12 Subunit p40; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D019707:Receptors, Chemokine; D012097:Repressor Proteins; C533289:SNFT protein, mouse; C493154:alpha-galactosylceramide
keywords: dendritic cell differentiation; differentiation of antigen presenting cells