Anatomic location and T-cell stimulatory functions of mouse dendritic cell subsets defined by CD4 and CD8 expression.
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.
McLellan
Alexander D
AD
Department of Dermatology, University of Würzburg, Joseph-Schneider Strasse 2, Würzburg 97080, Germany. alex.mclellan@mail.uni-wuerzburg.de
Kapp
Michaela
M
Eggert
Andreas
A
Linden
Christian
C
Bommhardt
Ursula
U
Bröcker
Eva-B
EB
Kämmerer
Ulrike
U
Kämpgen
Eckhart
E
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015704:CD4 Antigens / Q000032:analysis* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000145:classification / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D006649:Histocompatibility Antigens / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015704:CD4 Antigens; D016827:CD8 Antigens; D006649:Histocompatibility Antigens; D007519:Isoantigens