Interferon-producing Cells Fail to Induce Proliferation of Naive T Cells but Can Promote Expansion and T Helper 1 Differentiation of Antigen-experienced Unpolarized T Cells

Abstract

Interferon-producing cells (IPCs) secrete high levels of type I interferon in response to certain viruses. The lack of lineage markers, the expression of major histocompatibility complex (MHC) class II and the capacity to stimulate allogeneic T cells have led these cells to be classified as a subset of dendritic cells (DCs), called plasmacytoid DCs (PDCs). However, the role of IPCs/PDCs in initiating primary immune responses remains elusive. Here we examined the antigen presenting capacity of murine IPCs in antigen specific systems. While CD8α+ and CD11b+ DCs induced logarithmic expansion of naive CD4 and CD8 T cells, without conferring T helper commitment at a first encounter, primary IPCs lacked the ability to stimulate naive T cells. However, when antigen-experienced, nonpolarized T cells expanded by classical DC subsets, were restimulated by IPCs, they proliferated and produced high amounts of IFN-γ. These data indicate that IPCs can effectively stimulate preactivated or memory-type T cells and exert an immune-regulatory role. They also suggest that expansion of naive T cells and acquisition of effector function during antigen-specific T cell responses may involve different antigen-presenting cell (APC) types. Independent and coordinated control of T cell proliferation and differentiation would provide the immune system with greater flexibility in regulating immune responses.

Targeting Uptake Receptors on Human Plasmacytoid Dendritic Cells Triggers Antigen Cross-Presentation and Robust Type I IFN Secretion

“…In contrast, DEC-205 expression increases upon pDC activation and still efficiently captures Ags for subsequent processing and presentation (8). However, the delivery of Ag without TLR ligands as adjuvants would likely induce tolerogenic responses, because immature pDCs minimally express costimulatory molecules that are needed for T cell activation (31,32). Furthermore, our data support the importance of TLR ligands as adjuvants in the functional activation of CD8 + T cells, as pDCs pulsed with Ag alone did not induce IFNg-secreting T cells.…”

Viral infection and Toll‐like receptor agonists induce a differential expression of type I and λ interferons in human plasmacytoid and monocyte‐derived dendritic cells

“…Indeed, signaling downstream from TLR-9 leading to NF-‹ B activation appears to be completely dependent on MyD88 [33] whereas it has been reported that TLR-3 and TLR-4 activate NF-‹ B, IRF-3 and IRF-7 through the involvement of specific adaptor molecules [20,21,34]. In addition, it has been recently reported that in myeloid DC a TLR-independent mechanism for cytosolic doublestranded RNA recognition via PKR may induce high levels of type I IFN, indicating the complexity and variety of the type I IFN regulation in DC populations [35].…”

Probing in vivo dendritic cell functions by conditional cell ablation

“…65 In support of the notion that pDCs are poor APCs for naive T cells, pDCs do not endocytose antigens as efficiently as cDCs 88 and display low expression of two major cathepsins, which are involved in antigen processing. 89 However, notably in in vitro rechallenge experiments with nonstimulated, peptide-pulsed pDCs, memory CD4 + T cells proliferate and produce IFN-g. 90 In contrast to freshly isolated pDCs, in vitro preactivated pDCs augment cell surface expression of major histocompatibility complex class II and costimulatory molecules, increasing their T-cell stimulatory ability. This together with the fact that the cells were shown to upregulate the b-integrin CD11c has lead to the conclusion that the cells convert upon activation into cDC-like cells.…”