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J Leukoc Biol. 2014 Dec;96(6):1001-10. doi: 10.1189/jlb.1A0314-130R. Epub 2014 Aug 28.

Batf3-independent langerin- CX3CR1- CD8α+ splenic DCs represent a precursor for classical cross-presenting CD8α+ DCs.

Author information

1
Malaghan Institute of Medical Research, Wellington, New Zealand; and tpetersen@malaghan.org.nz.
2
Malaghan Institute of Medical Research, Wellington, New Zealand; and.
3
Malaghan Institute of Medical Research, Wellington, New Zealand; and School of Biological Sciences, Victoria University of Wellington, New Zealand.

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.

KEYWORDS:

dendritic cell differentiation; differentiation of antigen presenting cells

PMID:
25170118
DOI:
10.1189/jlb.1A0314-130R
[Indexed for MEDLINE]

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