The ability of murine dendritic cell subsets to direct T helper cell differentiation is dependent on microbial signals.
Dendritic cells (DC) initiate T cell responses and direct the class of T cell immunity through the production of Th-polarizing cytokines. In the mouse, immunization with CD8alpha(+) DC has led to Th1 priming whereas immunization with CD8alpha(-) DC has been associated with Th2 induction. Here, we use a direct T cell priming assay in vitro to re-examine the Th-directing potential of total DC or purified CD4(+) DC, CD8alpha(+) DC or CD4(-) CD8alpha(-) (double-negative; DN) DC subsets from mouse spleen. We show that the default Th effector phenotype induced by priming with DC depends on the protocol used for T cell purification, the T cell:antigen-presenting cell ratio and the antigen dose but is only marginally affected by DC subtype. All DC subsets can direct increased Th1 development in response to microbial stimuli known to elicit IL-12 production. Similarly, all subsets can suppress Th1 development and allow Th2 cellsto expand upon exposure to IL-10-inducing microbial agents. The flexibility of DC in directing Th development in function of microbial signals argues against the notion of pre-determined "DC1" and "DC2" subsets and suggests that multiple DC subtypes can direct an appropriate Th response to different classes of infectious agents.
Manickasingham
Shivanthi P
SP
Immunobiology Laboratory, Cancer Research UK, London Research Institute, London, GB.
Edwards
Alexander D
AD
Schulz
Oliver
O
Reis e Sousa
Caetano
C
D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology / Q000494:pharmacology; D000953:Antigens, Protozoan / Q000276:immunology / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000145:classification* / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology*
D000946:Antigens, Fungal; D000953:Antigens, Protozoan; D016753:Interleukin-10; D007371:Interferon-gamma