Functional analysis of dendritic cell–T cell interaction in sarcoidosis

Abstract

SummaryThe primary cause of the intense immune response in sarcoidosis is unclear. Potentially, a functional abnormality in dendritic cells (DCs) could cause a reduction in clearance of antigen and downstream persistence in immune activity. In this study, we investigate the interaction between monocytederived dendritic cells and T cells in patients with sarcoidosis compared to normal controls (n = 8 each) by examining the kinetics of autologous and allogeneic mixed leucocyte reactions over 9-10 days. We found markedly depressed proliferation kinetics in autologous DC-peripheral blood mononuclear cell (PBMC) co-cultures from sarcoid patients compared to normal subjects. In allogeneic experiments PBMCs from patients showed a reduced response to allogeneic DCs from a single donor, but no difference was observed in the ability of patients and control DCs to stimulate proliferation of allogeneic PBMC from a single donor. We conclude that there is a markedly impaired autologous mixed leucocyte reaction (MLR) in sarcoidosis patients. In allogeneic MLR, monocyte-derived DCs in sarcoidosis were able to stimulate T cells normally, but PBMCs responses were reduced. This contradicts recent published studies on ex vivo isolated myeloid DCs from sarcoidosis patients although, potentially, an in vivo conditioning factor, which reduces DC function in sarcoidosis, could be a unifying explanation for the contrasting findings.

Mapping mononuclear phagocytes in blood, lungs, and lymph nodes of sarcoidosis patients

“…MNPs are important in sarcoidosis both in activation and maintenance of pathogenic T cells as well as in contribution to granuloma formation by excessive TNF production by macrophages in the lungs of sarcoidosis patients . However, MNPs have mainly been studied in blood and BAL of sarcoidosis patients and generated heterogeneous data . This could partly be due to clinical heterogeneity among patients and limited differentiation between patients with acute and gradual disease onset.…”

“…25 However, MNPs have mainly been studied in blood and BAL of sarcoidosis patients and generated heterogeneous data. [26][27][28] This could partly be due to clinical heterogeneity among patients and limited differentiation between patients with acute and gradual disease onset. An important novelty of this study is the sideby-side investigation of MNP subsets in blood, BAL, EBBs, and LLNs Additionally, it is necessary to compare functional aspects of MNP subsets from sarcoidosis patients with MNPs from healthy controls as indicated in the different distribution ( Fig.…”

Myeloid-Derived Suppressor Cells Protect Islet Transplants by B7-H1 Mediated Enhancement of T Regulatory Cells

“…Our findings, in this study, demonstrated that induction of MDSC by HpSC was not MHC restricted since the HpSC from allogeneic and third party strains also induced similar levels of MDSC, which will definitely enhance the feasibility in clinical applications. To generate MDSC, HpSC from any source, such as surgical specimens or discarded liver donors, can be added into DC culture from patient peripheral blood mononuclear cells (PBMC), the protocol of which has well been established in cancer immunotherapy (20). It is also worthwhile to test whether human HpSC cell lines, such as LX-2, which was established by spontaneous immortalization in low serum condition (21), can be used for generation of MDSC.…”

Genome-wide association analysis reveals 12q13.3–q14.1 as new risk locus for sarcoidosis

“…In addition, it has recently been shown that OS9 interacts with the cytoplasmic tail of the dendritic cell-specific transmembrane protein during toll-like receptor-induced maturation of dendritic cells suggesting a role for OS9 in myeloid differentiation and cell fusion [52]. Dendritic cells have been discussed as important mediators of sarcoidosis immunology [53] and have been widely investigated with regards to various aspects of sarcoidosis [53][54][55][56].…”