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Blood, 15 March 2002, Vol. 99, No. 6, pp. 2084-2093

IMMUNOBIOLOGY

Anatomic location and T-cell stimulatory functions of mouse dendritic cell subsets defined by CD4 and CD8 expression

Alexander D. McLellan, Michaela Kapp, Andreas Eggert, Christian Linden, Ursula Bommhardt, Eva-B. Bröcker, Ulrike Kämmerer, and Eckhart Kämpgen

From the Department of Dermatology, Obstetrics and Gynecology, and Virology, University of Würzburg, Würzburg, Germany.

Mouse spleen contains CD4+, CD8alpha +, and CD4-/CD8alpha - dendritic cells (DCs) in a 2:1:1 ratio. An analysis of 70 surface and cytoplasmic antigens revealed several differences in antigen expression between the 3 subsets. Notably, the Birbeck granule-associated Langerin antigen, as well as CD103 (the mouse homologue of the rat DC marker OX62), were specifically expressed by the CD8alpha + DC subset. All DC types were apparent in the T-cell areas as well as in the splenic marginal zones and showed similar migratory capacity in collagen lattices. The 3 DC subtypes stimulated allogeneic CD4+ T cells comparably. However, CD8alpha + DCs were very weak stimulators of resting or activated allogeneic CD8+ T cells, even at high stimulator-to-responder ratios, although this defect could be overcome under optimal DC/T cell ratios and peptide concentrations using CD8+ F5 T-cell receptor (TCR)-transgenic T cells. CD8alpha - or CD8alpha + DCs presented alloantigens with the same efficiency for lysis by cytotoxic T lymphocytes (CTLs), and their turnover rate of class I-peptide complexes was similar, thus neither an inability to present, nor rapid loss of antigenic complexes from CD8alpha DCs was responsible for the low allostimulatory capacity of CD8alpha + DCs in vitro. Surprisingly, both CD8alpha + DCs and CD4-/CD8- DCs efficiently primed minor histocompatibility (H-Y male antigen) cytotoxicity following intravenous injection, whereas CD4+ DCs were weak inducers of CTLs. Thus, the inability of CD8alpha + DCs to stimulate CD8+ T cells is limited to certain in vitro assays that must lack certain enhancing signals present during in vivo interaction between CD8alpha + DCs and CD8+ T cells.

© 2002 by The American Society of Hematology.
 

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