Possible involvement of transglutaminase in endocytosis and antigen presentation

Experiments were carried out to determine as to whether or not internalization of antigen is necessary for subsequent antigen presentation by accessory cells using monoamines which are known as transglutaminase (TGase) inhibitors. It was found that endocytosis for immune complexes via Fc receptors such as sheep erythrocytes coated with IgG class antibody (EA) was different from receptor-independent endocytosis for soluble protein such as horse radish peroxidase (HRP) in the sensitivity to monoamines; methylamine inhibited the receptor-dependent endocytosis of immune complexes at a concentration of over 20 mM and the receptor-independent endocytosis of HRP at 2 mM, while dansylcadaverine (DC) inhibited both at a concentration of 100 microM. It was noteworthy that antigen-specific T cell proliferation to splenic adherent cells pulsed with DNP9.6-ovalbumin (DNP9.6-OVA) was blocked strongly by DC as well, but weakly by methylamine. These results suggest the possibility that antigen presentation requires internalization of antigen by a mechanism such as receptor-dependent endocytosis for the subsequent reexpression of antigen on membranes. Furthermore, it was confirmed that TGase activity is high in peritoneal exudate and spleen adherent cells, both of which have accessory cell activities for lymphocytes, suggesting the possibility that TGase might be involved intimately in receptor-dependent endocytosis and subsequent antigen presentation.     

Coexistence of fusion receptors for human T-cell leukemia virus type-I (HTLV-I) and human immunodeficiency virus type-1 (HIV-1) on MOLT-4 cells.

Human immunodeficiency virus type-1 (HIV-1) and human T-cell leukemia virus type-I (HTLV-I) have a similar tropism for target cell types, especially for CD4+ T cells. In this study, we provide evidence that receptors of these two viruses exist independently on the target cell. We established an HTLV-I-producing CD8+ T cell line (ILT-8M2) with a remarkable cell fusion capacity. When cocultured with MOLT-4 cells, ILT-8M2 cells induced giant syncytia more efficiently than any other tested HTLV-I-producer cell lines. In contrast to other HTLV-I-producers, ILT-8M2 cells were minimally susceptible to cytopathic effects of HIV-1 due to very low expression of CD4, although they were able to be persistently infected by HIV-1. The indicator MOLT-4 cells are known to respond well to HIV-1-induced cell fusion, but they lose this ability if they become persistently infected with HIV-1 because of the reduction of CD4 receptor expression. ILT-8M2 was, however, still capable of inducing syncytia with the MOLT-4 cells persistently infected by HIV-1 (MOLT-4/IIIB). This syncytium formation was dependent on the HTLV-I-envelope, as it was inhibited by HTLV-I-positive human sera or a monoclonal antibody to HTLV-I gp46 but not by monoclonal antibodies to HIV-1 gp120 or CD4. Moreover, ILT-8M2 cells persistently infected by HIV-1 (ILT-8M2/IIIB) induced both HTLV-I- and HIV-1-mediated syncytia with uninfected MOLT-4 cells. These results suggest that HTLV-I induces cell fusion utilizing receptors on the target cells independent of HIV-1-receptors.     

Synovial Mononuclear Cells Consist with T Cells Which Produce High Levels of Tumor Necrosis Factor α

To determine whether synovial mononuclear cells include a population of tumor necrosis factor α-produeing T cells, we measured tumor necrosis α levels in culture supernatants of synovial mononuclear cells by ELISA and analyzed tumor necrosis α mRNA-positive cell frequencies. There were no significant differences in the spontaneous levels of TNF α between synovial mononuclear cells and peripheral mononuclear cells. The frequency of tumor necrosis factor α mRNA-positive cells in synovial mononuclear cells was higher than that of peripheral mononuclear cells. When stimulated with a superantigen, mononuclear cells from the synovial fluid of rheumatoid arthritis patients showed higher levels of tumor necrosis factor α production (1,035 ± 817 pg/ml) than did mononuclear cells from their peripheral blood (236 ± 180 pg/ml). In addition, we observed that a few T cell clones were resistant to superantigenic restimulation in vitro. We conclude that when these types of T cells persist in the synovium, they play a role in the development of rheumatoid arthritis via a mechanism involving tumor necrosis factor α production.