The ability of murine dendritic cell subsets to direct T helper cell differentiation is dependent on microbial signals

Abstract

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 CD8α+ DC has led to Th1 priming whereas immunization with CD8α– 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, CD8α+ DC or CD4– CD8α– (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.

Mycobacterial heat shock protein 70 induces interleukin-10 production: immunomodulation of synovial cell cytokine profile and dendritic cell maturation

“…IL-10-producing APCs induce differentiation of T CD4 cells into IL-10-producing T cells [24]. In particular, the state of maturation of dendritic cells as well as the cytokines they produce are known to not only drive differentiation into TH1 or TH2 profiles [25,26], but also to ensue T cell tolerance or activation [27,28].…”

“…Responses were compared only among patients diagnosed with the same disease. For some experiments, blood was also obtained from healthy control volunteers who worked in the laboratory (mean age = 28, range [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] Peripheral blood mononuclear cell isolation Twenty ml of peripheral blood was collected by venepuncture in the morning (between 8 and 10 a.m) and samples stored into heparinized tubes. Synovial fluid (approximately 10 ml) was collected from all patients and diluted immediately 4 : 3 with phosphate buffered saline (PBS) and 15 m M EDTA before analysis.…”

Role of dendritic cells: a step forward for the hygiene hypothesis

“…[69][70][71][72][73] In mice, splenic CD8a 1 lymphoid DCs (DC1) were initially found to primarily promote a Th1 response, whereas the CD8a 2 myeloid DCs (DC2) were found to promote Th2 differentiation. 74,75 However, later studies challenged this one cell type-one type of response concept by showing that DCs with distinct functional properties may emerge from the same precursors, 76,77 and that CD8a 1 DCs could also play a regulatory role. Therefore, DCs are believed to be largely plastic in function, and the expression of costimulatory markers and cytokines/molecules is likely to be more important for characterizing functional DC subsets.…”

Parasite-Induced Th2 Polarization Is Associated with Down-Regulated Dendritic Cell Responsiveness to Th1 Stimuli and a Transient Delay in T Lymphocyte Cycling

“…One hypothesis, which has been considered heavily in the past, is that activation of different subsets of DC leads to differential Th1/Th2 commitment (30 -32). Nevertheless, more recent data argue that a requirement for different subsets is not absolute and that their influence can be overridden by appropriate external signals that are not subset specific (33)(34)(35). This process whereby microbial priming leads to DC with different Th1/Th2 polarizing potential has been termed conditioning.…”