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Biomedical subjects

T Sasazuki

Publications and source records attributed to T Sasazuki.

At least 127 records · Page 7Linked to original sources
PubMed1994

Segregation analysis of IgE responses to Cryptomeria japonica pollen antigen in vivo.

The IgE response to Cryptomeria japonica pollen antigen (CPAg) in vivo was determined by radioimmunoassay of the plasma of 525 members from 98 families with known nasal allergies. Based on responses, patients were classified into a non-responder or low-responder group (non/low) and a high-responder group. Segregation analysis revealed that the IgE non/low responsiveness to CPAg involved a single dominant trait. The gene frequency was calculated to be 0.44-0.60. The IgE non/low response to CPAg was found to be mediated by CPAg-specific suppressor T cells. These findings demonstrated that the phenotypic variation of IgE responsiveness to CPAg is not due the immune response gene, but rather is mediated by the immune suppression gene for CPAg, via CPAg-specific suppressor T cells.

Adolescent↗
PubMed1994

Role of human major histocompatibility complex DQ molecules in superantigenicity of streptococcus-derived protein.

Antigenicity of peptic extract from type 12 group A streptococci (PEAST12) for T cells was examined in major histocompatibility complex (MHC) class II transgenic mice. PEAST12 was mitogenic for murine T cells when antigen-presenting cells were obtained from human MHC (HLA)-DQ4 alpha beta transgenic mice or from DQ6 alpha beta transgenic mice but was not mitogenic in DR alpha transgenic, DR51 alpha beta transgenic, E alpha transgenic, or nontransgenic mice. In addition, PEAST12 showed mitogenicity for murine T cells in DQ4 alpha singly transgenic mice but not in DQ4 beta singly transgenic mice. T-cell stimulation by PEAST12 was unrestricted by but dependent on the expression of HLA-DQ molecules on antigen-presenting cells, and PEAST12 selectively activated T-cell receptor V beta 11-, V beta 15-, and V beta 18-positive T cells in mice. We propose that PEAST12 contains a superantigen which binds preferentially to the alpha-chain of HLA-DQ molecules. The well-known phenomenon that peptic extracts from group A streptococci are mitogenic in humans but not in mice is likely due to structural differences in MHC class II molecules between these two species of mammals.

Animals↗
PubMed1994

Identification of the disease-related T cell epitope of ovalbumin and epitope-targeted T cell inactivation in egg allergy.

An ovalbumin (OVA)-specific T cell line (TCL) was established from a patient with hen egg allergy. The TCL was CD4+, expressed alpha beta T cell receptor, and recognized OVA presented by HLA-DR10. Based on the response of the TCL to synthetic OVA peptides, it was found that the TCL recognized OVA 323-339, which is a major T cell epitope presented by murine I-Ad. The TCL secreted high levels of IL-5, but undetectable amounts of IL-2, interferon-gamma, and IL-4 when stimulated with OVA or the OVA 323-339 peptide. Since IL-5 is an important growth and chemotactic factor for eosinophils, it is possible that these OVA 323-339-specific T cells can contribute to human egg allergy. To our knowledge, this is the first demonstration of food allergen-specific TCL establishment and identification of a T cell epitope possibly related to the allergic reaction to food antigens. An analog peptide of the OVA 323-339 which is known to strongly bind to I-Ad partially inhibited the response of the TCL to OVA 323-339 presented by HLA-DR10, raising the possibility of peptide-based immunotherapy of food allergy.

Amino Acid Sequence↗
PubMed1994

Resistance to autoimmune thyroid disease is associated with HLA-DQ.

Genotypes of DQA1 and DQB1 genes were determined by polymerase chain reaction followed by dot blot hybridization with sequence-specific oligonucleotide probes in 105 patients with goitrous autoimmune thyroiditis (Hashimoto's thyroiditis) and in 67 patients with Graves' disease to investigate whether specific DQ alleles were associated with susceptibility or resistance to autoimmune thyroid diseases. Hashimoto's thyroiditis was found to be negatively associated with DQA1*0102 and DQB1*0602 whereas Graves' disease showed a negative association with DQB1*0501. No strongly positive association with a specific DQ allele was found in either disease. These results suggest that the HLA-DQ gene may be a genetic marker for resistance to autoimmune thyroid diseases.

Autoimmune Diseases↗
PubMed1994

HLA antigens in Japanese patients with systemic lupus erythematosus.

To determine the association of HLA antigens with SLE and the clinical findings of the disease, HLA antigens were tested in 58 Japanese patients with SLE, who fulfilled the ARA diagnostic criteria, along with 97 normal controls. HLA class I and II antigens were typed serologically using the antisera provided by the 11th HLA Workshop. Among the HLA class II antigens, further DRB, DQ and DP alleles were defined by DNA typing using the PCR/SSOP method. There were significantly more SLE patients with HLA-B39, DRB1*1501, DRB5*0101 and DQB1*0602 than normal controls. This result suggested that the haplotype of HLA-DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602 consists of the SLE-associated MHC markers in Japan. There were some positive and negative associations between the HLA antigens and clinical or serological findings in SLE. There is a possibility that some HLA alleles might be related to the clinical and/or serological subsets of SLE.

Alleles↗
PubMed1994

[Research trend for pathogenesis of sarcoidosis--streptococcal cell wall component (SCW)].

In search for the pathogenetic factors, we have found the following: 1) Chronic bacterial foci in the upper airway is showing adverse effect on clinical course of sarcoidosis. Alpha-streptococcus is mainly detected. 2) The prevalence of chronic tonsillitis in sarcoidosis is high if compared with that among Japanese adults examined by rhinolaryngologists. 3) The development of noncaseating epithelioid granulomas is reported after injections of an aqueous suspension of alpha-streptococcal cell wall (SCW) fragments into susceptible Lewis female rats. 4) Both protracted clinical course in sarcoidosis and higher responsiveness to SCW antigen are related to HLA-DR4, DR9 and DRw8. These results suggest that in sarcoidosis significance of persistence of antigen in upper respiratory tract and the significant correlation between SCW binding to Ia and immunogenicity, implicated by Schaeffer's, are seen.

Adult↗
PubMed1994

Genetic and immunological differences between Japanese patients with diffuse scleroderma and limited scleroderma.

OBJECTIVE: To study the association between HLA-DR and scleroderma (SSc), subsets of SSc, and autoantibodies in SSc. METHODS: HLA-DR antigens were determined in 45 Japanese patients with SSc. The association between HLA-DR and SSc, subsets of SSc, and autoantibodies was analyzed in 22 patients with SSc excluding mixed connective tissue disease (MCTD)/overlap syndrome (OL). RESULTS: When the 20 patients with MCTD and 3 patients with OL were excluded from the original patient group, a significant increase of HLA-DR2 was observed (59 vs 29% of controls, p < 0.01). The frequency of DR2 increased to 69% in patients with diffuse SSc (p < 0.01). DR1, which was not found in diffuse SSc, was found in 2 of 9 patients with limited SSc. The frequency of DR2 was significantly higher in patients with antitopoisomerase I (10/12, 83%, p < 0.05). In contrast, DR1 was found only in 2 patients with anticentromere antibodies (ACA), and all 5 patients with ACA had no HLA-DR2 (p < 0.01). CONCLUSION: Our results suggest that different HLA-DR markers may be associated with the production of distinct autoantibodies in diffuse SSc and limited SSc.

Antibodies↗
PubMed1993

A missense mutation of cardiac beta-myosin heavy chain gene linked to familial hypertrophic cardiomyopathy in affected Japanese families.

A novel missense mutation of the cardiac beta-myosin heavy chain gene was detected in five unrelated Japanese patients and their affected family members with hypertrophic cardiomyopathy (HCM) by using the polymerase chain reaction (PCR)-DNA conformation polymorphism (DCP) analysis. Sequencing analysis revealed an A to G transition at codon 778 leading to replacement of the Asp residue, which is adjacent to the interaction sites of myosin heavy chain (MHC) with actin and is a conserved amino acid residue in various MHC across species, to the Gly residue. Linkage study of the mutation and two dinucleotides repeat markers of the cardiac beta-MHC gene in three affected families showed that the mutation was on the same haplotype of the cardiac beta-MHC gene and linked to HCM. These observations strongly suggest that the 778Asp to Gly mutation is the cause of HCM in these affected individuals.

Actins↗
PubMed1993

Altered growth of human colon cancer cell lines disrupted at activated Ki-ras.

Point mutations that activate the Ki-ras proto-oncogene are presented in about 50 percent of human colorectal tumors. To study the functional significance of these mutations, the activated Ki-ras genes in two human colon carcinoma cell lines, DLD-1 and HCT 116, were disrupted by homologous recombination. Compared with parental cells, cells disrupted at the activated Ki-ras gene were morphologically altered, lost the capacity for anchorage-independent growth, grew more slowly both in vitro and in nude mice, and showed reduced expression of c-myc. Thus, the activated Ki-ras gene plays a key role in colorectal tumorigenesis through altered cell differentiation and cell growth.

Animals↗
PubMed1993

Restricted expression of transgenic HLA-DRA gene in thymic epithelial cells and its role in acquisition of T cell tolerance to self-superantigens and processed DR alpha-derived peptide.

We have established a set of transgenic mouse lines in which the HLA-DRA gene was expressed in different cell types. In one line (DR alpha-24), DR alpha E beta b molecules were expressed on thymic medullary and cortical epithelial cells and all lineages of bone marrow-derived antigen-presenting cells (APC) except for thymic macrophages. By contrast, expression of the molecules in another line (DR alpha-30) was found on thymic medullary and cortical epithelial cells but not on bone marrow-derived APC in the thymus and periphery. To evaluate the role of thymic epithelial cells in acquisition of T cell tolerance, comparative analysis of DR alpha-24 and DR alpha-30 was performed. In DR alpha-30, T cells expressing TcR V beta 5 and V beta 11 were eliminated to comparable levels to those in DR alpha-24, suggesting that expression of the DR alpha E beta b molecules on thymic epithelial cells are sufficient for clonal deletion of the self-superantigen-reactive T cells. In addition, CD4+ T cells from DR alpha-30 as well as those from DR alpha-24 were tolerant to DR alpha-derived peptide/I-Ab complex expressed on spleen cells from DR alpha-24 even in the presence of exogenous interleukin-2. These observations suggest that expression of the DR alpha chain in thymic epithelial cells could induce T cell tolerance directed toward naturally processed DR alpha-derived peptide bound to I-Ab molecules, probably via clonal deletion of the self-reactive T cells.

Animals↗
PubMed1993

Generation of a novel CD8+ cytotoxic T lymphocyte that requires soluble factor to lyse autologous antigen-presenting cells.

We reported the existence of high and low responders to the streptococcal cell wall antigen (SCW) in the human population. To analyze the mechanism of the low responsiveness to SCW at the cellular level, we established SCW-specific CD4+ T cell lines. During the course of generation of a SCW-specific CD4+ T cell line restricted by HLA-DQ from a low responder, we obtained autoreactive CD8+ cytotoxic T lymphocytes as a cell line (HYCD8). They proliferated in the presence of autologous monocytes and IL-2, without SCW. HYCD8 lysed autologous monocytes and Epstein-Barr virus-transformed B lymphoblastoid cell line (BLCL). This cytotoxic activity was specifically inhibited by an anti-HLA class I framework monoclonal antibody and restricted by HLA-B52 or B54 specificity, as judged by killing activity against panel cells and HLA class I-transfected BLCL. It was unique to HYCD8 that the HLA class I-restricted cytotoxicity was observed only in the presence of soluble factor with low molecular mass (< 10(4) Da) produced mainly by B cells, which could not be replaced by known cytokines and their mixtures. We thus describe novel HLA class I-restricted cytotoxic CD8+ T cells that kill antigen-presenting cells in a soluble factor-dependent manner.

Antibodies, Monoclonal↗
PubMed1993

T-cell repertoire in a strain of transgenic C57BL/6 mice with the HLA-DRA gene on the X-chromosome.

We have established a strain of transgenic mice in which the HLA-DRA gene was integrated into the X-chromosome and the xenogeneic mixed isotype molecule, DR alpha E beta b, was expressed in a cell type-specific manner, although the transgenic DRA gene contained only 268 base pairs of the 5'-flanking region. The DR alpha E beta b molecules expressed in the transgenic mice functioned as major histocompatibility complex (MHC) class II to select T-cell repertoire, and to stimulate mixed lymphocyte reaction. In female transgenic mice homozygous for HLA-DRA (DR alpha-B6-F-homo) and male transgenic mice (DR alpha-B6-M), DR alpha E beta b molecules were expressed in almost all of the MHC class II Ab-positive cells. In contrast, the expression of DR alpha E beta b molecules in female transgenic mice hemizygous for HLA-DRA (DR alpha-B6-F-hemi) was found only in part of the Ab positive cells, and the proportion of cells expressing the DR alpha E beta b molecules varied due to random inactivation of one of the X-chromosomes. Clonal deletions of the T cells and mature thymocytes bearing Tcrb-V5 and Tcrb-V11, which are eliminated from the peripheral repertoire in mice expressing self-superantigen and MHC class II E molecules, were incomplete in DR alpha-B6-F-hemi as compared with those in DR alpha-B6-F-homo, and were correlated with the proportion of DR alpha E beta b-positive spleen cells. These observations suggested that the number of bone marrow-derived cells expressing DR alpha E beta b molecules was critical for clonal deletions of Tcrb-V5+ and Tcrb-V11+ T cells in the thymus.

Animals↗