CD4+ T Cells Have a Key Instructive Role in Educating Dendritic Cells in Allergy

Abstract

Background: Dendritic cells (DCs) are central in allergy as regulators of the Th1/Th2 balance. We have recently demonstrated a unique transcriptional profile of DCs in patients with ongoing allergy compared with healthy subjects and shown that crosstalk between DCs and memory T cells affects the transcriptional profile of T cells. However, the transcriptional profile of DCs educated by T cells in allergy is unknown. Methods: In the present study, we have examined the transcriptional profiles of DCs after stimulation with grass pollen allergens, Phleum pratense and coculture with autologous CD4+ memory T cells using high-density microarray. Protein analysis was performed using flow cytometry and recombinant antibody protein microarrays. Patients with allergic rhinitis and healthy subjects were compared. Results: The results reveal a distinct T-cell-induced DC profile in atopic individuals. Accordingly, about 170 genes were upregulated and 40 genes downregulated. For example, the chemokine receptor CXCR4 and the tumor necrosis factor receptor CD30 were upregulated in DCs derived from atopic donors, and this could also be verified at the protein level. Conclusion: We conclude that crosstalk between CD4+ memory T cells and autologous DCs induces transcriptional reprogramming in DCs. This finding suggests that T cells have a key instructive role in educating DCs in Th2-type responses.

Antibacterial antibody responses associated with the development of asthma in house dust mite-sensitised and non-sensitised children

“…The sustained Th2 response to colonising bacteria could downregulate Th1 and Th17 responses which could also have a role in the production of disease 22. The second is that the IgE antibody itself can enhance antigen capture via Fcε receptors on antigen-presenting cells and increase the recruitment of antibacterial T cells which, on balance, have been shown to be polarised to Th1,23 and these could alter the education of dendritic cells and hence signals to allergen-specific T cells 24. The inverse association of the IgE to Der p 1 and Der p 2 with the antibacterial IgE points to a downregulation of the anti-allergen Th2 response.…”

The crucial role of dendritic cells in rhinitis

“…Moreover, CD30 (TNF receptor) and MMP25 were up-regulated in blood-monocyte-derived dendritic cells when subjected to memory T-cell co-culture. ICOSL up-regulation occurred exclusively in educated dendritic cells from allergic patients [31]. Furthermore, nasal mucosal tissue T cells clearly produced IFN-g in CRS patients [32].…”

“…In-vitro studies of dendritic cell/T-cell interaction indicate that memory CD4þ T cells can change the transcriptional profile of dendritic cells. Blood memory CD4 T cells can educate dendritic cells and induce the up-regulation and down-regulation of several genes, which can be independent of the allergic status of the patient [31]. Moreover, CD30 (TNF receptor) and MMP25 were up-regulated in blood-monocyte-derived dendritic cells when subjected to memory T-cell co-culture.…”

Th17 responses are not altered by natural exposure to seasonal allergens in pollen-sensitive patients

“…Expression of C–C chemokine receptor type 7 (CCR7, CD197) on memory T cells enables distinguishing of central memory T cells (CD45RA− CCR7+), which are able to migrate to the lymph nodes and stimulate dendritic cells, from effector memory T cells (CD45RA− CCR7−), which possess effector functions and can migrate to the inflammatory site [11]. Transcriptional activation of dendritic cells caused by interaction with memory T cells and increased T cell proliferation after culturing with allergen-stimulated dendritic cells in patients suffering from allergic rhinitis has been described by Larsson et al [12]. After secondary stimulation, central memory T cells lose their CCR7 receptor and acquire effector function becoming effector memory T cells [11].…”