Characterization of a new subpopulation of mouse CD8alpha+ B220+ dendritic cells endowed with type 1 interferon production capacity and tolerogenic potential.
We describe a new B220+ subpopulation of immaturelike dendritic cells (B220+ DCs) with low levels of expression of major histocompatibility complex (MHC) and costimulatory molecules and markedly reduced T-cell stimulatory potential, located in the thymus, bone marrow, spleen, and lymph nodes. B220+ DCs display ultrastructural characteristics resembling those of human plasmacytoid cells and accordingly produce interferon-alpha after virus stimulation. B220+ DCs acquired a strong antigen-presenting cell capacity on incubation with CpG oligodeoxynucleotides, concomitant with a remarkable up-regulation of MHC and costimulatory molecules and the production of interleukin-12 (IL-12) and IL-10. Importantly, our data suggest that nonstimulated B220+ DCs represent a subset of physiological tolerogenic DCs endowed with the capacity to induce a nonanergic state of T-cell unresponsiveness, involving the differentiation of T regulatory cells capable of suppressing antigen-specific T-cell proliferation. In conclusion, our data support the hypothesis that B220+ DCs represent a lymphoid organ subset of immature DCs with a dual role in the immune system-exerting a tolerogenic function in steady state but differentiating on microbial stimulation into potent antigen-presenting cells with type 1 interferon production capacity.
Martín
Pilar
P
Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain; and Faculté de Médecine Pasteur, INSERM U364, Nice, France.
Del Hoyo
Gloria Martínez
GM
Anjuère
Fabienne
F
Arias
Cristina Fernández
CF
Vargas
Héctor Hernández
HH
Fernández-L
Africa
A
Parrillas
Verónica
V
Ardavín
Carlos
C
D000818:Animals; D016827:CD8 Antigens / Q000032:analysis; D002454:Cell Differentiation; D019070:Cell Lineage / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D007108:Immune Tolerance / Q000276:immunology*; D016130:Immunophenotyping; D007370:Interferon Type I / Q000096:biosynthesis / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice / Q000276:immunology*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D019707:Receptors, Chemokine / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D016827:CD8 Antigens; C431698:CD8alpha antigen; D007370:Interferon Type I; D019707:Receptors, Chemokine; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1