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.

SummaryProstaglandin E 2 (PGE 2 ), a major lipid derived from the metabolism of arachidonic acid, is an environmentally bioactive substance produced by inflammatory processes and acts as a cAMP up-regulator that plays an important role in immune responses. It has been reported that PGE 2 has the ability to inhibit the production of interleukin-12 by myeloid dendritic cells (MDCs) and macrophages, and then induce preferential T helper type 2 (Th2) cell responses. However, little is known of the function of PGE 2 for plasmacytoid dendritic cells (PDCs), which may contribute to the innate and adaptive immune response to viral infection, allergy and autoimmune diseases. In the present study, we compared the biological effect of PGE 2 on human PDCs and MDCs. PGE 2 caused the death of PDCs but MDCs survived. Furthermore, we found that, whereas PGE 2 inhibited interferon-a production by PDCs in response to virus or cytosine-phosphate-guanosine, it inhibited interelukin-12 production by MDCs in response to lipopolysaccharide (LPS) or poly(I:C). Although both virus-stimulated PDCs and LPS-stimulated MDCs preferentially induced the development of interferon-c-producing Th1 cells, pretreatment with PGE 2 led both DC subsets to attenuate their Th1-inducing capacity. These findings suggest that PGE 2 represents a negative regulator on not only MDCs but also PDCs.

A search for HLA haplotypes of a family of five indicated that four members had the same haplotype. Systemic lupus erythematosus (SLE) had already developed in three of these four people. SLE has now developed in the remaining person, and the result is that all the members of the family having the same haplotype will develop SLE. Regarding these four SLE patients, the types of autoantibodies and the symptoms were different in each person, so the idea that this haplotype is strongly related to the onset of SLE but minimally related to the symptoms was suggested.

The pathophysiology of cGVHD still remains unclear. To gain more insight into the immunological mechanism of cGVHD, we examined surface marker and cytokine production of peripheral blood T cells from 19 patients in the chronic phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median age of patients was 31 years (range 13–47 years). The median days from allo-HSCT to examination was 43 months (range 17–94 months). Ten patients in whom 6 have treated with immunosuppressive agents and 4 without them developed chronic GVHD, whereas 9 patients in whom 5 have treated with immunosuppressive agents and 4 without them did not develop chronic GVHD. Peripheral blood mononuclear cells were extracted from patients and 10 healthy volunteers, followed by isolation into CD4+ T cells and CD8+ T cells. The analysis of surface marker and intracellular cytokine production of these cells was performed using fluorescence activated cell sorter. The percentage of IFN-g-producing CD8+ T cells among CD8+ T cells was significantly higher in patients with or without cGVHD than in healthy volunteers (p<0.001). Since all 19 patients were in remission, the IFN-g-producing CD8+ T cells might be related to graft-versus-leukemia effect. On the other hand, the percentage of IL-4-producing CD8+ T cells among CD8+ T cells was significantly higher in patients with cGVHD (mean 3.3%, range 1.3–8.2%) than in patients without cGVHD (mean 1.2%, range 0.8–1.7%) and healthy volunteers (mean 1.1%, range 0.1–1.6%) (both p<0.001). By contrast, the percentage of IL-4-producing CD4+ T cells was not different among patients with and without cGVHD and healthy volunteers. Then, we minutely explored the immunological role of IL-4-producing CD8+ T cells in healthy volunteers. These cells expressed the surface marker of CD25, CCR4 and CTLA-4. In the analysis of cytokine production in these cells, we identified the type 2 cytokine, such as IL-4, IL-5, IL-10, and IL-13, although we could not find IFN-g. In conclusion, these findings suggest that IL-4-producing CD8+ T cells may be an immunological marker of cGVHD in which these cells may play a crucial role as regulatory T cells.

A search for HLA haplotypes of a family of five indicated that four members had the same haplotype. Systemic lupus erythematosus (SLE) had already developed in three of these four people. SLE has now developed in the remaining person, and the result is that all the members of the family having the same haplotype will develop SLE. Regarding these four SLE patients, the types of autoantibodies and the symptoms were different in each person, so the idea that this haplotype is strongly related to the onset of SLE but minimally related to the symptoms was suggested.