Dendritic cells (DCs) show a functional plasticity in determining Th responses depending on their maturational stage or on maturational signals delivered to the DCs. Human plasmacytoid DCs (PDCs) can induce either Th1- or Th2-type immune responses upon exposure to viruses or IL-3, respectively. In this study we have investigated the Th-polarizing capacity of PDCs after short (24-h) or long (72-h) culture with stimuli and have assessed the expression and function of OX40 ligand (OX40L) in PDC-mediated Th polarization in addition to type I IFN-dependent responses. IL-3-treated PDCs expressed OX40L, but produced almost no IFN-α in response to T cell stimulation (CD40 ligand or T cell interaction), resulting in the preferential priming of Th2 cells through OX40L-dependent mechanisms. Meanwhile, PDCs were rapidly endowed by viral infection (Sendai virus) with a high potency to develop IFN-γ-producing Th cells depending on their capacity to residually produce IFN-α. Although Sendai virus-stimulated PDCs simultaneously expressed OX40L in their maturational process, the Th1-inducing effect of endogenous type I IFNs may overcome and thus conceal the OX40L-dependent Th2 responses. However, during maturation in response to Sendai virus over the longer 72-h period, the expression level of OX40L was up-regulated, whereas the residual IFN-α-producing ability was down-regulated, and consequently, the PDCs with prolonged Sendai virus stimulation induced Th2 responses to some extent. Thus, PDCs have the distinct means to dictate an appropriate response to environmental stimuli.

Background: Sarcoidosis is a systemic granulomatous disease of unknown aetiology. It has been suggested that T helper type 1 (Th1) polarisation is associated with the pathophysiology of sarcoidosis, but the mechanism of skewing towards Th1 has not been elucidated. Dendritic cells (DCs) are known to regulate immune responses. This study was performed to determine whether DCs are involved in the aetiology of sarcoidosis. Methods: The numbers of peripheral blood DCs in 24 patients with sarcoidosis were analysed and biopsy specimens from four patients were stained immunohistochemically using monoclonal antibodies. Results: The numbers of both myeloid and lymphoid DC subsets were significantly decreased in the blood and mature DCs were found in the granulomas of patients with sarcoidosis. A number of interferon-c (IFNc) producing T cells were also detected in the sarcoid granuloma, as well as many interleukin (IL)-4 producing T cells. Double staining of the biopsy specimen using anti-fascin and anti-CD3 antibodies showed an anatomical interaction between DCs and T cells. Conclusions: These findings suggest that the blood DC subsets may migrate into the affected tissues, contributing to the formation of the granulomas in sarcoidosis. It is hypothesised that the migrating DCs may regulate the T cell response in sarcoidosis, at least in the granulomatous lesions.

We present a case of proliferative glomerulonephritis with peculiar IgM deposition associated with sarcoidosis. A 62-year-old woman, who had been diagnosed with sarcoidosis 3 years previously because of abnormalities on chest X-ray radiophotographs and lymph node pathology, was admitted to our hospital for the evaluation of proteinuria and microscopic hematuria. Laboratory findings showed renal dysfunction (creatinine clearance, 52 ml/min), a moderate range of urinary protein (1.51 g/day), and increased serum lysozymes (20.7 microg/ml; normal range, 3.4-8.6 microg/ml). Serum calcium level was within the normal range. Renal biopsy revealed immune complex glomerulonephritis (IgM deposition type) with a membranoproliferative pattern, without granuloma or calcium deposition. Corticosteroid (initial dose of prednisolone [PSL], 1 mg/kg per day) was administered, but neither renal function nor urinary protein improved. She then became nephrotic and her renal function gradually deteriorated. To our knowledge, among uncommon glomerulonephritides with sarcoidosis, five cases of immune complex glomerulonephritis with IgM deposition have been reported. Immune complex glomerulonephritis with IgM deposition is unusual and could be related to sarcoidosis; it may be a characteristic pathology which could provide a clue to elucidate the pathogenesis of sarcoidosis.