ARG098, a novel anti-human Fas antibody, suppresses synovial hyperplasia and prevents cartilage destruction in a severe combined immunodeficient-HuRAg mouse model

<p>Abstract</p> <p>Background</p> <p>The anti-human Fas/APO-1/CD95 (Fas) mouse/human chimeric monoclonal IgM antibody ARG098 (ARG098) targets the human Fas molecule. The cytotoxic effects of ARG098 on cells isolated from RA patients, on normal cells <it>in vitro</it>, and on RA synovial tissue and cartilage <it>in vivo </it>using implanted rheumatoid tissues in an SCID mouse model (SCID-HuRAg) were investigated to examine the potential of ARG098 as a therapy for RA.</p> <p>Methods</p> <p>ARG098 binding to each cell was analyzed by cytometry. The effects of ARG098 on several cells were assessed by a cell viability assay <it>in vitro</it>. Effects on the RA synovium, lymphocytes, and cartilage were assessed <it>in vivo </it>using the SCID-HuRAg mouse model.</p> <p>Results</p> <p>ARG098 bound to cell surface Fas molecules, and induced apoptosis in Fas-expressing RA synoviocytes and infiltrating lymphocytes in the RA synovium in a dose-dependent manner. However, ARG098 did not affect the cell viability of peripheral blood mononuclear cells of RA patients or normal chondrocytes. ARG098 also induced apoptosis in RA synoviocytes and infiltrating lymphocytes in the RA synovium <it>in vivo</it>. The destruction of cartilage due to synovial invasion was inhibited by ARG098 injection in the modified SCID-HuRAg mouse model.</p> <p>Conclusions</p> <p>ARG098 treatment suppressed RA synovial hyperplasia through the induction of apoptosis and prevented cartilage destruction <it>in vivo</it>. These results suggest that ARG098 might become a new therapy for RA.</p

Entanglement entropy of two disjoint intervals and the recursion formula for conformal blocks

We reconsider the computation of the entanglement entropy of two disjoint intervals in a (1+1) dimensional conformal field theory by conformal block expansion of the 4-point correlation function of twist fields. We show that accurate results may be obtained by taking into account several terms in the operator product expansion of twist fields and by iterating the Zamolodchikov recursion formula for each conformal block. We perform a detailed analysis for the Ising conformal field theory and for the free compactified boson. Each term in the conformal block expansion can be easily analytically continued and so this approach also provides a good approximation for the von Neumann entropy

Abnormally High Levels of Virus-Infected IFN-γ+CCR4+CD4+CD25+ T Cells in a Retrovirus-Associated Neuroinflammatory Disorder

BACKGROUND:Human T-lymphotropic virus type 1 (HTLV-1) is a human retrovirus associated with both HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which is a chronic neuroinflammatory disease, and adult T-cell leukemia (ATL). The pathogenesis of HAM/TSP is known to be as follows: HTLV-1-infected T cells trigger a hyperimmune response leading to neuroinflammation. However, the HTLV-1-infected T cell subset that plays a major role in the accelerated immune response has not yet been identified. PRINCIPAL FINDINGS:Here, we demonstrate that CD4(+)CD25(+)CCR4(+) T cells are the predominant viral reservoir, and their levels are increased in HAM/TSP patients. While CCR4 is known to be selectively expressed on T helper type 2 (Th2), Th17, and regulatory T (Treg) cells in healthy individuals, we demonstrate that IFN-gamma production is extraordinarily increased and IL-4, IL-10, IL-17, and Foxp3 expression is decreased in the CD4(+)CD25(+)CCR4(+) T cells of HAM/TSP patients as compared to those in healthy individuals, and the alteration in function is specific to this cell subtype. Notably, the frequency of IFN-gamma-producing CD4(+)CD25(+)CCR4(+)Foxp3(-) T cells is dramatically increased in HAM/TSP patients, and this was found to be correlated with disease activity and severity. CONCLUSIONS:We have defined a unique T cell subset--IFN-gamma(+)CCR4(+)CD4(+)CD25(+) T cells--that is abnormally increased and functionally altered in this retrovirus-associated inflammatory disorder of the central nervous system