Characterization of an Immediate Splenic Precursor of CD8(+) Dendritic Cells Capable of Inducing Antiviral T Cell Responses

Bedoui, S; Prato, S; Mintern, J; Gebhardt, T; Zhan, Y; Lew, AM; Heath, WR; Villadangos, JA; Segura, E

Author(s): Bedoui, S; Prato, S; Mintern, J; Gebhardt, T; Zhan, Y; Lew, AM; Heath, WR; Villadangos, JA; Segura, E;
Details: Publication Year 2009-04-01,Volume 182,Issue #7,Page 4200-4207
Journal Title: JOURNAL OF IMMUNOLOGY
Publication Type: Journal Article
Abstract: Mouse spleens contain three major dendritic cell (DC) populations: plasmacytoid DC, conventional CD8(+)CD24(+) DC (CD8(+) DC), and conventional CD8(-)CD24(-) DC (CD8(-) DC). We have previously shown that CD8(+) DC are the major cross-presenting subtype in vivo and are the main inducers of antiviral cytotoxic T lymphocyte responses. Here we show that after depletion of CD8(+) DC, the only DC capable of viral Ag presentation was a small subset that expresses CD24 but not CD8. This CD8(-)CD24(+) DC population is greatly expanded in mice treated with the DC growth factor FMS-like tyrosine kinase 3 ligand. The CD8(-)CD24(+) DC represent an immediate precursor of CD8(+) DC, as demonstrated by their expression pattern of characteristic markers of CD8(+) DC, their capacity to cross-present in vitro, and their conversion into CD8(+) DC upon adoptive transfer into recipient mice. Accordingly, the lifespan of transferred CD8(-)CD24(+) DC in vivo was greatly enhanced as compared with terminally differentiated CD8(+) DC. Moreover, in a vaccination protocol, CD8(-)CD24(+) DC induced stronger T cell responses and accelerated viral clearance of HSV-1 compared with CD8(+) DC. Our results demonstrate that the ability to cross-present first appears in an immediate precursor population of CD8(+) DC that does not yet express CD8. The enhanced capacity of CD8(-)CD24(+) DC to induce immune responses upon adoptive transfer makes them an attractive novel tool for DC-based immunotherapies. The Journal of Immunology, 2009, 182: 4200-4207.
Publisher: AMER ASSOC IMMUNOLOGISTS
Keywords: ANTIGEN-PRESENTING FUNCTIONS; HERPES-SIMPLEX VIRUS; SUBSETS IN-VIVO; CROSS-PRESENTATION; CUTTING EDGE; LANGERHANS CELLS; STEADY-STATE; CD8-ALPHA(+); IMMUNITY; MOUSE
Publisher's Version: https://doi.org/10.4049/jimmunol.0802286
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2009-04-01 12:00:00