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K Yui

Publications and source records attributed to K Yui.

At least 73 records · Page 4Linked to original sources
PubMed1990

Self-reactive T cells can escape clonal deletion in T-cell receptor V beta 8.1 transgenic mice.

To study the mechanisms of tolerance in detail, we have constructed transgenic mice expressing a V beta 8.1-D beta 2-J beta 2.3-C beta 2 T-cell receptor (TCR) gene. Since expression of V beta 8.1 is known to correlate with reactivity of CD4+CD8- T cells to minor lymphocyte-stimulating locus 1a (Mls-1a), we expected to induce tolerance in most CD4+CD8- T cells in V beta 8.1 transgenic mice of the Mls-1a allele. In one line of Mls-1b V beta 8.1 transgenic mice, the V beta 8.1 TCR was expressed on greater than 98% of mature T cells and their response to Mls-1a was highly enriched. In Mls-1a V beta 8.1 transgenic mice, CD4+CD8- T cells in these mice were severely reduced among both peripheral T cells and thymocytes. However, the deletion of these cells was not complete, and most of the residual CD4+CD8- mature T cells still expressed normal densities of V beta 8.1 TCR. The residual CD4+CD8- T cells did not respond to Mls-1a but were still able to proliferate in response to other stimuli via the TCR. Interestingly, CD4+CD8- V beta 8.1+ T-cell clones isolated from Mls-1a V beta 8.1 transgenic mice could respond to Mls-1a. We suggest that these types of T cells escape clonal deletion in the thymus.

Animals↗
PubMed1990

Mechanisms of autoimmunity in the context of T-cell tolerance: insights from natural and transgenic animal model systems.

There are a number of mechanisms which cooperate to produce and maintain T-cell tolerance. First, and perhaps most important, is the clonal deletion in the thymus of T cells with high affinity for self antigens. However, to ensure that a wide repertoire of T cells is available in the periphery to combat foreign antigens, the threshold of clonal deletion may be set low enough so that T cells whose TCR's have sub-threshold affinity for self antigens mature and migrate to the periphery. T cells which recognize self antigen-derived peptides not expressed or presented in the thymus will also fail to be deleted. For those self-reactive T cells which are not deleted in the thymus, other mechanisms may produce tolerance, including an undefined alteration of signalling pathways which produces clonal anergy, and lowering the avidity of the TCR for its ligand by downregulating coreceptor and accessory molecules. Active suppression of T-cell responses in another well-described phenomenon whose mechanism is undefined. From our observations with the model systems discussed here, we have observed three distinct mechanisms by which T-cell tolerance can be circumvented, allowing autoimmune phenomena to occur. These mechanisms may have relevance for different types of autoimmune diseases seen in humans. In gld mice, the autoimmune disease seems to be related to a global defect in T-cell differentiation and function, which allows for the expansion of autoimmune B cells. While we showed that clonal deletion of V beta-bearing T cells is appropriate in certain cases, aberrant lymphokine secretion by the abnormal T cells or disruption of immune system regulation are most probably responsible for allowing autoantibody production. While human lupus erythematosis shares much of the pathology of lpr and gld mice, there is no expansion of T cells with a similar phenotype in human lupus. There are environmental factors which must play a role in the development of human lupus, since the incidence of the disease does not follow an absolute genetic pattern. The escape from clonal deletion and subsequent reactivation of autoimmune T cells which we observed in V beta 8.1 TCR-transgenic mice can be a model for human autoimmune diseases such as multiple sclerosis and type I diabetes, in which T cells are directed against a specific autoantigen. According to this model, susceptibility loci for autoimmune disease such as the MHC would function by producing different repertoires of T cells which in some cases could gain autoreactivity following activation.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1989

Major histocompatibility complex class I-specific cytolytic T cells, derived from gld mice, lacking Thy-1, CD4, and CD8.

Thy-1 is a major cell surface molecule expressed on murine thymocytes and peripheral T cells. Its physiological function is unknown, but in vitro studies suggest that Thy-1 may transmit activation signals to T cells and may play a role in the growth and/or differentiation of thymocytes [Kroczek, R. A., Gunter, K. C., Seligmann, B. & Shevach, E. M. (1986) J. Immunol. 136, 4379-4384; Kroczek, R. A., Gunter, K. C., Germain, R. N. & Shevach, E. M. (1986) Nature (London) 322, 181-184]. However, not all mouse thymocytes are Thy-1+ [Scollay, R., Wilson, A., D'Amico, A., Kelly, K., Egerton, M., Pearse, M., Wu, L. & Shortman, K. (1988) Immunol. Rev. 104, 81-120]. In addition, C3H-gld/gld mice accumulate large numbers of Thy-1- (and Thy-1+) T-cell antigen receptor-positive CD8- CD4- (double negative) T cells in peripheral lymphoid organs. Our previous studies of these Thy-1- and Thy-1+ double negatives suggested that lack of Thy-1 expression correlated with diminished capacity to respond to T-cell stimuli. In this report, we describe a Thy-1- alpha/beta T-cell receptor-positive major histocompatibility complex-specific cytotoxic T-cell clone derived from C3H-gld/gld lymph node-residing cells. The data show that, at least in this system, Thy-1 (and CD8/CD4) expression is not required for growth, cytolytic activity, or expression of functional T-cell receptor complexes in vitro and raise the possibility that Thy-1 expression may not be obligatory in vivo for development of cytotoxic T-lymphocyte precursors in gld mice.

Animals↗
PubMed1987

Characterization of Lyt-2-, L3T4- class I-specific cytolytic clones in C3H-gld/gld mice. Implications for functions of accessory molecules and programmed development.

We report the first demonstration of Thy-1+, Lyt-2-, L3T4- MHC-specific CTL clones derived from the Lyt-2-, L3T4- subset of lymph node cells of C3H-gld/gld mice. These clones express alpha/beta heterodimeric TCRs on the cell surface and specifically recognize class I molecules on target cells. Lyt-2 and L3T4 molecules are therefore not essential for the induction, recognition, and killing of antigen-specific CTL. In addition, these studies suggest that antigen specificity development for class I structures may occur before Lyt-2 gene activation in the differentiation of T cells.

Animals↗
PubMed1987

T-cell receptor genes in autoimmune mice: T-cell subsets have unexpected T-cell receptor gene programs.

Two unique cell subsets have been identified in the autoimmune-prone MRL/MP lpr/lpr and C3H/HeJ gld/gld murine strains that have the Lyt-2-,L3T4-,Thy-1+, and Lyt-2-,L3T4-,Ia-,Thy-1- phenotypes, respectively. We have now found that these cells express T-cell receptor proteins on their surface. Our observations further indicate that the expression of the Thy-1 antigen does not correlate with the expression of alpha-chain and beta-chain T-cell receptor polypeptides. Interestingly, T-cell receptor gamma-chain RNA expression may be influenced or correlate with Thy-1 molecular expression. These studies indicate unusual relationships of different cell-surface structures that may reflect unexpected developmental programs.

Animals↗
PubMed1986

Cellular FITC-linked immunospecific assay (cell-FLISA) for detection of monoclonal antibodies against cell-surface antigens.

A cellular fluorescein isothiocyanate (FITC)-linked immunospecific assay (Cell-FLISA) has been established using the recently developed fluorophotometer for microplates. In the Cell-FLISA system, monoclonal antibodies specific for the surface antigens of live cells are detected by measuring the fluorescence intensity of an FITC-labeled second antibody: goat anti-mouse immunoglobulin antibody. It takes only 2 min to count 96 samples in microplate wells using the fluorophotometer for microplates. Moreover, by this system, the analysis is finished within 2 hr. Thus, the Cell-FLISA system has advantages in screening a large number of samples, such as hybridoma cell lines secreting monoclonal antibodies against cell-surface antigens.

Animals↗
PubMed1985

Activation of immunoglobulin allotype-specific T cells by B cells.

To investigate the role of Ia and immunoglobulin (Ig) molecules of B cells in alloantigen-specific and nominal antigen-specific T-cell activations, the ability of B cells to stimulate Ig allotype-specific T cells was examined. T15-primed B10.BR T cells responded to MOPC 315 (IgA myeloma protein derived from BALB/c) as well as T15 but not to MOPC31c (IgG1 myeloma protein). These T cells were stimulated by papain-digested Fc fragment of T15. Thus, T15-primed B10.BR T cells were shown to be specific for Ig allotype of T15, that is, Igh-2a. T15-specific B10.BR T cells were selected by 10-day cultures with T15 in vitro. They responded to BALB.K spleen cells without addition of soluble T15 antigen to the assay culture. Stimulator cells in this mixed lymphocyte reaction (MLR)-like response between T15-specific B10.BR T cells and BALB.K spleen cells were Thy-1-, Ia+ cells and these responses were blocked by anti-Iak antibodies. Furthermore, Sephadex G-10-passed BALB.K B cells stimulated the proliferation of T15-specific B10.BR T cells, while they failed to stimulate allogeneic BALB/c spleen cells. The stimulating ability of B cells in this MLR-like response of T15-specific B10.BR T cells was shown to be genetically restricted, namely, both H-2 and non-H-2 genes are involved in the manifestation of the stimulating ability. This system will provide a useful model for studying the role of B-cell surface Ig and Ia molecules in the activation of antigen-specific T cells and alloreactive T cells.

Animals↗
PubMed1985

Phylogenetic hierarchy of antigen-presenting ability in antigen-specific T cell activation.

The phylogenetic hierarchy of antigen-presenting ability was shown to exist in xenogeneic mouse, rat and human T cell-antigen-presenting cell (APC) interaction. The antigen-presenting ability of human APC is dominant over that of rat APC and the ability of rat APC is dominant over that of mouse APC. The HLA-DR molecule was shown to function for antigen presentation to PPD-specific autologous human and xenogeneic murine T cells.

Animals↗
PubMed1984

Interspecies cross-reactivity of Class II antigen of MHC determined by syngeneic, allogeneic and xenogeneic B and T cells.

Although this chapter ought to summarize the role of MHC antigens in T cell activation, the immunobiological meaning of the polymorphism of Class II antigens, as well as that of Class I antigens, is still unresolved. The antigen-presenting ability of human APC is dominant over that of murine APC in the stimulation of antigen-specific xenogeneic T cells. In addition, xenoreactive murine T cells specific for human PBL failed to recognize the polymorphic determinant of Class II antigens of human MHC. On the basis of the data, Class II antigens may be seen to have some role as antigen-presenting molecules rather than as restricting molecules, at least, in the xenogeneic APC-T cell interaction or the xenogeneic MLR responses. These data together with the fact that the linkage disequilibrium found among the various groups of alleles encoding Class I and II antigens making up an MHC haplotypes suggest that the MHC may play a key role during evolution. These studies using xenogeneic cell interaction may shed some light on the immunobiological function of polymorphism of MHC antigens in the mechanisms of T cell activation, and the evolutional history of the polymorphism of the NHC in self or not-self recognition by T cells.

Animals↗
PubMed1984

Serological cross-reactivities of murine and human class II antigen determined by murine xeno anti-human class II antibody.

Murine anti-human class II antibodies were shown to cross-react with polymorphic determinants of murine class II antigens. The cross-reacting antibodies were raised in B10.S(9R) mice by immunizing with human nylon wool adherent cells (Ad cells) from peripheral blood leukocytes. The B10.S(9R) anti-human Ad cell antiserum bound to the molecules consisting of two chains with molecular weights of 35K and 28K dimers which were purified with a lentil-lectin column. The B10.S (9R) anti-human class II antiserum was also revealed to contain two distinct cross-reacting antibodies with polymorphic determinants of murine class II antigens coded for by the I-A subregion of the H-2. One is specific for a determinant of class II molecules coded for by I-Ab,d,q, and the other seems to be specific for class II molecules coded for by I-Aa,k,r.

Animals↗
PubMed1983

Immune response to Toxoplasma gondii. I. Toxoplasma-specific proliferation response of peripheral blood lymphocytes from patients with toxoplasmosis.

Peripheral blood leukocytes (PBL) from patients with toxoplasmosis were shown to be highly responsive to in vitro stimulation with Toxoplasma gondii extract as measured by incorporation of [3H]methylated thymidine. Analysis of Toxoplasma-specific proliferative cells in PBL by using monoclonal antibodies specific for human T cell subsets revealed that the Toxoplasma-specific proliferation response of PBL from the patients was mediated by Leu 1, Leu 3a positive cells, that is, helper/inducer T cells. Tests for the Toxoplasma-specific proliferation response may provide a readily available method for the diagnosis of congenital toxoplasmosis, especially during the newborn period.

Antibodies, Monoclonal↗
PubMed1983

Antigen-specific proliferation responses of peripheral blood lymphocytes to Trichomonas vaginalis antigen in patients with Trichomonas vaginitis.

This report describes the development of an assay system which overcomes the difficulty of detecting immune responses of patients with Trichomonas vaginitis by making use of peripheral blood leukocytes obtained from such patients. When peripheral blood leukocytes from the patient were stimulated in microcultures with the soluble antigen extracted from Trichomonas vaginalis, significant degrees of proliferation ensued, as measured by the incorporation of [methyl-3H]thymidine 4 to 5 days after initiation. The antigen-induced proliferation response of peripheral blood leukocytes is specific for T. vaginalis antigen. The T. vaginalis-specific [methyl-3H]thymidine incorporation is mediated by Leu-1-positive cells, namely, T lymphocytes, in the peripheral blood leukocyte population. This assay system should prove useful for the analysis of the immune response to the protozoa in patients with Trichomonas vaginitis.

Antigens↗
PubMed1983

Early changes in ornithine decarboxylase activity and polyamines during erythroid differentiation of Friend leukemia cells.

Induction of cytosolic L-ornithine decarboxylase (ODC) activity in cultures of Friend erythroleukemia cells by seeding in fresh medium was suppressed by treatment with several differentiation inducers. The levels of suppression after 3 h treatment were about 60% at 20 mM nicotinamide, 30% at 1.5% dimethyl sulfoxide (DMSO), and 20% at 5 mM hexamethylene bisacetamide (HMBA). Tracer experiments using [3H]ornithine to determine newly accumulated polyamines including putrescine revealed that the accumulation was suppressed by treatment (18 h) with the inducers. Furthermore, results of polyamine determination by high-pressure liquid chromatography showed that the cellular polyamine content in differentiation-induced cells was lower than those of uninduced cells in early (18 h after inducer treatment) stages of differentiation. Accordingly, it is suggested that cytosolic ODC levels virtually represent the rate of accumulation of intracellular polyamines in the early period of differentiation.

Animals↗
PubMed1983

Immune response to Trichomonas vaginalis. IV. Immunochemical and immunobiological analyses of T. vaginalis antigen.

The immune response of patients with trichomoniasis vaginitis to Trichomonas vaginalis was examined by using passive hemagglutination assay and skin reactions. Trichomonas-specific immune responses could hardly be detected in the patients by these assay methods. In order to develop a simple and reliable assay for demonstration of T. vaginalis-specific immune responses in the patients, proliferation responses of peripheral mononuclear cells from the patients were examined. Lymphocytes obtained from the patients were shown to incorporate 3H-methyl-thymidine when stimulated with T. vaginalis antigen in vitro. Furthermore, immunochemical analysis of T. vaginalis antigen has been done by Sephadex chromatography and sodium dodecyl sulfate gel electrophoresis. The data revealed that the murine and human IgM antibodies specific to T. vaginalis recognize various antigens with a wide range of molecular weights (between 13,000 and 100,000 daltons), while human and murine IgG antibodies recognize molecules with a much narrower range of molecular weights (50,000-100,000 daltons).

Antibodies↗
PubMed1982

Role of glycolysis in the tension development under anoxia in guinea pig taenia coli.

The role of glycolysis in the tension development under anoxic conditions in a high-K medium was studied in the intestinal smooth muscle of guinea pig taenia coli. After exposure to the high-K medium (isotonic, 60 mM) under normal oxygen for 30 min, the muscles were exposed to a high-K medium bubbled with N2 gas. The tonic contraction decreased gradually to about 10% of the original level. Glucose was then cumulatively added to the high-K medium under anoxia. The maximum tension was observed following the addition of the higher concentrations of glucose. The muscle tension which developed in the high-K medium with a high concentration of glucose under anoxia was dependent on the external Ca2+ and was inhibited by iodoacetic acid (IAA). The addition of glucose to a high-K medium under anoxia also increased lactate release from the muscle. Pretreatment with 1 mM IAA decreased the lactate release from the muscle. In a Ca2+-free medium under anoxia, the addition of glucose did not increase the muscle tension although there was a significant increase in the lactate release. In summary, it is considered that the smooth muscle of taenia coli develops tension utilizing energy produced by the glycolytic pathway under anoxia in a high-K medium.

Animals↗