Immature dendritic cells (CD11c+ CD3- B220- cells) present in mouse peripheral blood

It is well known that dendritic cells (DCs) are developed from the peripheral blood of mice when peripheral blood mononuclear cells (PBMCs) are cultured with GM-CSF. We have previously found that immature DCs are present in the blood even in humans. In the present study, we show that CD11c+ CD3- B220- cells in the mouse peripheral blood are immature DCs. The percentage of CD11c+ CD3- B220- cells in the (PBMCs) of normal mice ranges from 0.5 to 2.5%. The CD11c+ CD3- B220- cells in the PBMCs show dendrites, similar in shape to the CD11c+ CD3- B220- cells in the spleen, which are thought to be DCs definitely. However, they have practically no capacity to stimulate the proliferation of allogeneic T cells, and show a lower expression of MHC class II, B7-1 and B7-2 than CD11c+ CD3- B220- cells in the spleen. When the CD11c+ CD3- B220- cells in the PBMCs are cultured with GM-CSF, they show not only the potent ability to stimulate the proliferation of allogeneic T cells but also a higher expression of MHC class II, B7-1 and B7-2. Moreover, they migrate into the spleen when they are injected intravenously. These results suggest that CD11c+ CD3- B220- cells in the PBMCs are immature DCs, and that they migrate into the spleen, where they mature.     

Oligomeric immunoglobulin A antibody response to rubella virus infection.

Pooled sera from rubella patients in the early convalescent stage, containing a high titer of hemagglutination-inhibiting (HI) antibody, were treated with protein A-conjugated gel to reduce immunoglobulin G (IgG) antibody and then centrifuged in sucrose gradients. This treatment resulted in the detection of an HI activity peak sedimenting at a rate intermediate between 7S and 19S. In contrast to the 19S antibody, the HI activity of this peak was not abolished by 2-mercaptoethanol, but sedimented at 7S after this treatment. The activity was considered to consist of IgA oligomers, since it was removed by anti-IgA immunosorbent. The appearance of the oligomeric IgA antibody after the infection was then studied using serum samples collected sequentially from five rubella patients. Shortly after the onset of the disease, the HI activity appeared at high titer and thereafter gradually decreased in titer until it could no longer be detected in the sera. The time of its disappearance varied with each patient.     

TGF-β1 Null Mutation Leads to CD154 Upregulated Expression in Affected Tissues

The TGF-1(–/–) mouse is a murine model for systemic autoimmune disease. The aim of this study is to elucidate the immunological mechanism that leads to multifocal tissue inflammation and autoantibody production in TGF-1(–/–) mice. Heart, lung, liver, and salivary gland from TGF-1(–/–) were assessed for CD154 expression by RT-PCR and immunohistochemistry. Compared to wild-type littermates, CD154 expression was elevated in all tissues studied. Furthermore, IL-12 mRNA was expressed in the salivary gland and heart of TGF-1(–/–) mice and not in wild-type littermates. This suggests that the CD154 pathway is activated in these tissues. This shows that TGF-1 regulates CD154 expression leading to spontaneous IL-12 production and autoimmunity.     

Role of CD4 molecule in intrathymic T-cell development.

We have investigated the role of CD4 molecules in intrathymic T-cell repertoire selection. The administration of monoclonal antibody (mAb) to CD4 in organ culture of murine foetal thymus (FTOC) completely inhibited the development of CD4+8- cells, and additional treatment with anti-class II MHC (Ia) mAb caused no further effects on this inhibition. On the other hand, when the potentially autoreactive cells in Mls-1a mice were monitored by expression of the Mls-1a-reactive V beta 6 gene product of T-cell receptor alpha beta (TcR alpha beta), the treatment with anti-CD4 resulted in the appearance of V beta 6-bearing cells to some extent, but this effect was considerably reinforced by the combinatory use of anti-Ia mAb with anti-CD4. In a model system where the bacterial superantigen staphylococcal enterotoxin B serves as self-antigen to deplete V beta 8-bearing cells in FTOC, the depletion of V beta 8+ cells was restored partially by anti-CD4 alone but completely by the combination with anti-Ia. These results suggest that CD4 is indispensable for positive selection of all CD4+8- thymocytes, whereas participation of CD4 in negative selection is only partial. It was also observed that the development of TcR alpha beta-bearing cells in the CD4-8- population was inhibited by the treatment with anti-CD4 mAb. In Mls-1a mice, V beta 6-bearing cells were developed in CD4-8+, CD4+8+, and also in CD4-8- populations after anti-CD4 mAb treatment. It is suggested that TcR alpha beta-bearing CD4-8- cells are possibly originated from CD4+ cells and undergo CD4-mediated thymic selection.     

Experimental osteodystrophy of chronic renal failure induced by aluminum- and ferric-nitrilotriacetate in Wistar rats

The aluminum (Al) and iron (Fe) chelate complexes of nitrilotriacetate (NTA) cause renal insufficiency when they are administered intraperitoneally to rats. Their effects on bone metabolism were studied in 4 week old Wistar rats. Daily intraperitoneal administration of Al-NTA (3 mg Al/kg for 11 weeks) induced osteomalacia, impaired bone growth, decreased bone mineral density, lower serum PTH levels than normal as well as renal insufficiency. Al staining showed diffuse deposition in the trabecula and a strong linear band of aluminum deposited at the mineralization front and along the cement line. The osteoid seen markedly within the trabecula was probably the decalcified portion of the bone, the calcium apatite of which was defectively fabricated because of diffuse Al deposition in the trabecula. Al deposition along the cement line would make it much more susceptible to external shear stress than normal. Although daily intraperitoneal administration of Fe-NTA (6 mg Fe/kg for 11 weeks) caused impaired bone growth, decreased bone mineral content and renal insufficiency, the osteoid volume did not increase. Fe staining showed that Fe was deposited diffusely in the cytoplasm of osteoblasts. The results of this study demonstrated that during renal insufficiency, different minerals exhibi different modes of action on bone metabolism, and that AI-NTA is useful for experimental animal models of Al-induced osteomalacia in renal insufficiency.