Biomedical subjects

J Koide

Publications and source records attributed to J Koide.

At least 37 records · Page 2Linked to original sources

PubMed1991

The presence of anti-protein A antibodies in patients with rheumatoid arthritis.

Sixteen patients with rheumatoid arthritis (RA) were examined for the presence of anti-protein A antibodies. The F(ab')2 preparations from five RA patients showed significant binding to IgG-free protein A on ELISA. The protein A binding was further examined by immunoblotting. The F(ab')2 preparations of high protein A-binding protein gave a specific reaction with IgG-free protein A on nitrocellulose paper. This demonstrates the presence of anti-protein A antibodies in patients with RA. Those RA patients with anti-protein A antibodies had more active disease as judged by the Lansbury's activity index. The level of serum rheumatoid factor (RAHA) was significantly higher in patients with anti-protein A antibodies than in those without anti-protein A antibodies.

Adult↗

PubMed1991

[Morphological study of cochlea in experimental chronic serum sickness].

Relationship of circulating immune complexes to some inner ear disorders has been suggested recently. Thus, bovine serum albumin (BSA) nephritis, a model of chronic serum sickness, was made and morphological, immunological studies of cochlea were performed using light microscopy, transmission electron microscopy and immunofluorescent antibody methods. Group 1 consisted of animal sensitized with daily BSA injections for 90 days; in group 2, BSA was administered for 70 days, daily, and after a three-weeks interval, injections were continued for another 21 days; group 3 consisted of animals sensitized with daily BSA injections for 100 days followed by BSA injection into the facial nerve via the stylo-mastoid foramen. The animals (group 3) were sacrificed on day 1 and 4 following facial nerve sensitization for examination of cochlear morphological changes. No morphological changes were observed (group 1). Protrusion of marginal cells into endolymphatic space was seen, because of swelling of endoplasmic reticulum of the cells of stria vascularis's (group 2). Slight hydrops was present mainly in the basal turn (group 3). No IgG deposits were found in all groups. It appears that the changes in group 2 were caused by rather chronic nephritis than immune reaction. We conclude that damage induced in the cochlea is negligible compared to the extensive lesions observed in the kidney in chronic serum sickness.

Animals↗

PubMed1990

Alloantigen-specific cytotoxic clones bearing the alpha,beta T cell antigen receptor but not CD4 or CD8 molecules.

The vast majority of circulating lymphocytes that express the alpha,beta TCR in association with CD3 also express either CD4 or CD8 molecules, which are thought to act as important accessory structures in HLA class II- and I-restricted T cell functions, respectively. In the current study alpha,beta TCR+ clones devoid of detectable CD4 or CD8 were generated by repeated stimulation of fresh CD3+,CD4-,CD8- cells with an allogeneic lymphoblastoid cell line in the presence of conditioned medium containing IL-2. Except for the absence of CD4 and CD8, which was associated with undetectable levels of CD4 and CD8 mRNA, the clones were phenotypically indistinguishable from classical CD3+,alpha,beta TCR+ cells. Furthermore, they mediated potent cytolysis of their specific stimulator line but did not kill irrelevant LCL or NK-sensitive targets. mAb to CD3 and the alpha,beta TCR inhibited cytolysis, suggesting that the clones use the TCR/CD3 complex to recognize and respond to their targets. mAbs to CD2 and CD11a also inhibited cytolysis, indicating that the clones use these accessory molecules to interact with their targets. Finally, cytolysis was inhibited by an HLA-A,B,C framework-specific mAb (W6/32) as well as a mAb (MA2.1) specific for an HLA-A2 epitope. These results demonstrate that CD3+,alpha,beta TCR+,CD4-,CD8- cytotoxic clones can be generated from the peripheral blood of healthy adults, and use their TCR/CD3 complexes to function in an HLA class I-restricted manner.

Antigens, CD↗

PubMed1990

Differences in surface phenotype and mechanism of action between alloantigen-specific CD8+ cytotoxic and suppressor T cell clones.

We have previously demonstrated that fresh CD8+ T cells proliferate in response to autologous, alloantigen-primed CD4+ T cells, and differentiate into Ts cells, which inhibit the response of fresh T cells to the primary allogeneic stimulator cell but not irrelevant stimulators. Although such Ts do not have discernible cytolytic activity, like classical cytotoxic T cells (Tc) they express CD3 and CD8 on their surface and function in a class I MHC-restricted manner. Our study was an attempt to compare the surface phenotype and mechanism of action of Ts and Tc clones derived from the same individual. Ts clones were generated from donor JK by repeated stimulation of CD8+ T cells with an autologous CD4+ T inducer line specific for an allogeneic lymphoblastoid cell line (LCL). These clones were noncytolytic for either the inducer line or the allogeneic stimulator LCL. Tc clones, generated by direct stimulation of JK CD8+ T cells with the same allogeneic LCL, mediated potent, alloantigen-specific cytolysis. All Tc clones were alpha, beta TCR+, CD3+, CD4-, CD8+, CD11b-, and CD28+. Ts clones were also alpha, beta TCR+, CD3+, and CD8+, but in contrast to Tc clones, Ts clones were CD11b+ and CD28-. When added to MLR both Ts and Tc clones inhibited the response of fresh JK CD4+ T cells to the original but not irrelevant allogeneic LCL. However, Ts inhibited the response of only those CD4+ T cells that shared class I)MHC determinants with the Ts donor, whereas Tc inhibited the response of CD4+ T cells from all responders, regardless of HLA type. Pretreatment of Ts clones with mAb to CD2, CD3, or CD8 blocked suppression, whereas similar pretreatment of Tc clones blocked cytotoxicity in 4-h 51Cr release assays but had no effect on Tc-mediated suppression of the MLR. These results suggest that both Ts and Tc clones can inhibit the MLR but they do so through different mechanisms. Moreover, the maintenance of distinct surface phenotypes on these long term clones suggests that Ts may be a distinct sublineage of CD8+ T cells rather than a variant of CD8+ Tc.

Antigen-Antibody Reactions↗

PubMed1990

Thrombotic thrombocytopenic purpura in two patients with systemic lupus erythematosus: clinical significance of anti-platelet antibodies.

Thrombotic thrombocytopenic purpura (TTP) is a clinical syndrome of unknown etiology and has a high mortality rate due to disseminated platelet thrombi. However, the mechanism of platelet agglutination is not understood. Although an immunological mechanism has been suggested as the basis for the pathogenesis of TTP, any possible immune-mediated etiology remains unclear. The association of TTP with systemic lupus erythematosus (SLE) affords a unique opportunity to study such possibilities, because SLE is a prototype of autoimmune disease. This report describes two patients with SLE who developed TTP. The development of anti-platelet antibodies is one possible immunological mechanism for platelet agglutination in patients with SLE complicated by TTP. More importantly, patient J.Y., who had anti-platelet antibodies, responded dramatically to high doses of prednisolone.

Adult↗

PubMed1990

[NK-like cytotoxicity of allospecific gamma delta TCR+ T cell clones].

We recently generated a series of human alloantigen-specific, CD3+, gamma delta- TCR+ clones by stimulating CD3+, CD4-, CD8- T cells from normal individuals with allogeneic lymphoblastoid cell lines (LCL). These clones display cytotoxic activity against their specific stimulators but not against irrelevant LCL. Most but not all of these clones express the NK cell associated marker, CD57, and kill NK-sensitive targets such as the K562 and Molt 4 lines, but not NK-resistant line, Raji. Gamma delta clones which lacked expression of CD57 had no detectable NK activity. The allospecific cytotoxicity of CD57+ and CD57- clones was inhibited by mAb to CD3 or the TCR delta- chain. In contrast, the NK-like activity of the CD57+ clones was enhanced by these antibodies over a wide range of antibody concentration. An HLA class I framework-specific mAb had no effect on NK-like cytolysis but did inhibit allospecific killing, suggesting that the target structures on the surface of allospecific and NK-sensitive cells are distinct. The receptors utilized by the gamma delta- TCR+ clones to recognize NK-sensitive and allospecific targets are also distinct, since killing of NK-sensitive targets was blocked by the presence of cold (unlabeled) NK-sensitive cells but not by cold allospecific targets, whereas allospecific cytolysis was inhibited by cold allospecific targets but not by NK-sensitive cells. We conclude that some CD3+, TCR- gamma delta+ clones exhibit NK-like as well as allospecific killing and that these two activities are mediated by distinct receptor-ligand interactions.

B-Lymphocytes↗

PubMed1989

Natural killer (NK)-like cytotoxic activity of allospecific T cell receptor-gamma,delta+ T cell clones. Distinct receptor-ligand interactions mediate NK-like and allospecific cytotoxicity.

We recently generated a series of human alloantigen-specific, CD3+,TCR-gamma,delta+ clones by stimulating CD3+,CD4-,CD8- T cells from normal individuals with allogeneic lymphoblastoid cell lines (LCL). As reported previously, these clones display cytotoxic activity against their specific stimulators but not against irrelevant LCL. Further studies of these and other TCR-gamma,delta+ clones, described in this report, indicate that most but not all of these clones express the NK cell associated marker, NKH-1 or Leu-19, and kill NK-sensitive targets such as the K562 and Molt 4 lines, but not an irrelevant LCL or NK-resistant line, Raji. TCR-gamma,delta+ clones which lacked expression of Leu-19 lysed their allospecific targets but had no detectable NK activity. The allospecific cytotoxicity of Leu-19+ and Leu-19- clones was inhibited by mAb to CD3 or the TCR delta-chain. In contrast, the NK-like activity of the Leu-19+ clones was enhanced by these antibodies over a wide range of antibody concentration. Although mAb to LFA-1 markedly inhibited both the allospecific and NK-like activity of these clones, an HLA class I framework specific mAb (W6/32) had no effect on NK-like cytolysis but did inhibit allospecific killing, suggesting that the target structures on the surface of allospecific and NK-sensitive cells are distinct. The receptors utilized by the TCR-gamma,delta+ clones to recognize NK-sensitive and allospecific targets are also distinct, since killing of NK-sensitive targets was blocked by the presence of cold (unlabeled) NK-sensitive cells but not by cold allospecific targets, whereas allospecific cytolysis was inhibited by cold allospecific targets but not by NK-sensitive cells. We conclude that some CD3+,TCR-gamma,delta+ clones exhibit NK-like as well as allospecific killing and that these two activities are mediated by distinct receptor-ligand interactions.

Adult↗

PubMed1989

Differences in surface phenotype between cytolytic and non-cytolytic CD4+ T cells. MHC class II-specific cytotoxic T lymphocytes lack Leu 8 antigen and express CD2 in high density.

A number of cell surface molecules are differentially expressed on functionally distinct subsets of CD4+ T cells. However, to date CD4+ T cells capable of becoming CTL have not been shown to be phenotypically distinct from other CD4+ T cells, and in the current study we examined the ability of Leu 8+ and Leu 8- CD4+ subpopulations to become cytotoxic effectors after their stimulation with allogeneic lymphoblastoid cell lines. Although CD4+, Leu 8+ cells proliferated more vigorously than CD4+, Leu 8- cells in primary cultures stimulated with allogeneic LCL, the CD4+, Leu 8- population was the major source of cytotoxic effectors, killing targets with specificity for their class II MHC alloantigens. In most subjects, CD4+ precursors of CTL were distinguished not only by their lack of Leu 8 expression but also by their relatively high density of CD2, LFA-1, and LFA-3, molecules known to mediate non-specific cell-to-cell adhesion and postulated to be markers of immunologic memory. The absence of Leu 8 does not appear to be a reliable memory cell marker, however, because Leu 8+ as well as Leu 8-, CD4+ cells from PPD skin test positive subjects responded to the recall Ag, PPD. During 3 mo of continuous culture with allogeneic stimulators, Leu 8- cells retained their cytolytic activity and remained unreactive with anti-Leu 8 mAb, whereas Leu 8+ cells remained non-cytolytic and reactive with anti-Leu 8, suggesting that under the conditions used the Leu 8 phenotype is relatively stable. PHA or anti-CD3 mAb enhanced non-specific killing by alloantigen-stimulated CD4+,Leu 8- lines but failed to unmask any cytolytic potential in CD4+,Leu 8+ lines. We conclude that MHC class II-specific cytolytic CD4+ T cells can be distinguished from non-cytolytic CD4+ cells on the basis of their surface phenotype, and that most CD4+ CTL are contained within the Leu 8- subpopulation.

Animals↗

PubMed1989

Evidence for involvement of the gamma, delta T cell antigen receptor in cytotoxicity mediated by human alloantigen-specific T cell clones.

The vast majority of mature T cells express the alpha, beta TCR and use this receptor to recognize Ag in association with MHC determinants. Recent reports indicate that a small subpopulation of CD3+ T cells does not express alpha, beta TCR and lacks CD4 and CD8 molecules, but expresses another TCR heterodimer designated gamma, delta. To date, however, there are very few examples of gamma, delta TCR-bearing T cells which have Ag-specific functions and the precise role of the gamma, delta TCR remains unknown. In an attempt to explore the function of the gamma, delta TCR in man, we generated a panel of CD3+, CD4-, CD8- T cell clones from cultures of normal T cells stimulated with allogeneic lymphoblastoid cell line (LCL). All of the clones stained with mAb to gamma, delta TCR determinants, and Northern blot analysis of total cellular RNA revealed mature gamma- and delta-chain transcripts and immature beta-chain transcript. The clones displayed cytolytic activity against their specific stimulating LCL, but not irrelevant LCL, and killing was inhibited by a mAb to HLA class I (HLA-A,B,C) determinants, suggesting that these cells recognized class I MHC antigenic determinants on specific stimulator/target cells. Cytolysis by these clones was markedly inhibited by low concentrations (0.00001 to 0.001 microgram/ml) of mAb to CD3 or TCR delta-chain, but high concentrations (0.1 to 20 micrograms/ml) of the same antibodies enhanced cytotoxicity. When absorbed to plastic tissue culture wells, anti-CD3 mAb stimulated the clones to proliferate. These results indicate that alloantigen specific, gamma, delta TCR+, CD4-, CD8- T cell clones can be reproducibly generated in vitro, and that the gamma, delta TCR plays a direct role in the specific recognition and cytolysis displayed by these clones.

Adult↗

PubMed1989

CCA [N-(2-carboxyphenyl)-4-chloroanthranilic acid disodium salt], a newly developed immunomodulating drug, suppresses T-cell activation by acting on macrophages.

The cellular mechanism of action of a newly developed drug, CCA, N-(2-carboxyphenyl)-4-chloroanthranilic acid disodium salt, on PHA-, autologous mixed lymphocyte reaction (AMLR)-, and phorbol myristate acetate (PMA)-stimulated T-cell proliferation was investigated. Addition of 50 micrograms of CCA per milliliter suppressed PHA- and AMLR-stimulated T-cell proliferation. In contrast, CCA failed to suppress PMA-stimulated macrophage-depleted T-cell proliferation. After treatment of T cells or macrophages with CCA for 12 h, recombined T cells and macrophages were stimulated with phytohemagglutinin. [3H]Thymidine incorporation by T cells was suppressed when macrophages but not T cells were treated with CCA. These results indicate that CCA suppresses T-cell proliferation by acting on macrophages. The mechanism involved in this suppression of CCA was due to the loss of Ia antigen on macrophages and the loss of interleukin-1 (IL-1) secretion from macrophages.

Adjuvants, Immunologic↗

PubMed1988

CD4 molecules are associated with the antigen receptor complex on activated but not resting T cells.

To explore the relationship between CD4 and CD3/Ti on the T cell surface, we have studied a panel of Ag-specific Th cell lines and clones, as well as resting and mitogen-activated CD4+ cells. Our results show that exposure of Th cells to their specific antigenic stimuli, but not to irrelevant stimuli, induced the rapid disappearance of approximately 20 to 35% of CD3 and CD4 molecules. The modulation of these molecules was detected in less than 1 h, became maximal at 12 h, and recovered thereafter in parallel. Treatment of Th cells with anti-CD4 antibody prevented Ag-induced modulation of CD3, and treatment with anti-CD3 blocked modulation of CD4. In the absence of Ag, treatment of these cells with an antibody (WT-31) directed at a conformational determinant within CD3/Ti or with the combination of anti-CD3 antibody and goat anti-mouse Ig, also resulted in significant modulation of CD4. Similar treatment of PHA-activated CD4+ T cells with anti-CD3/Ti antibodies also induced CD4 modulation; however, the same antibodies failed to affect CD4 expression on fresh resting T cells. These results indicate that on activated, but not resting T cells, CD4 molecules can be physically associated with CD3/Ti. We postulate that this association is essential for efficient Th cell activation, and further that the ability of anti-CD4 antibodies to inhibit helper functions is due to their prevention of CD4-CD3/Ti interaction on the T cell surface.

Antigen-Antibody Reactions↗

PubMed1988

Cellular regulation of anti-nRNP antibody synthesis is different from that of anti-DNA antibody synthesis in patients with systemic lupus erythematosus.

The cellular regulation of anti-nuclear ribonucleoprotein (nRNP) antibody synthesis in patients with systemic lupus erythematosus (SLE) was examined and compared with that of anti-double-stranded DNA (dsDNA) antibodies. In vitro antibody production by lymphocytes from SLE patients with antibodies to either dsDNA or nRNP alone was measured using dsDNA-specific and nRNP-specific solid-phase radioimmunoassays (RIA). Lymphocytes of SLE patients with only anti-dsDNA antibodies and normal individuals failed to synthesize anti-nRNP antibody with or without nRNP stimulation. In contrast, lymphocytes from SLE patients with anti-nRNP antibody alone in their sera synthesized in vitro a large amount of anti-nRNP antibody with or without nRNP stimulation. Experiments with reconstituted autologous lymphocytes indicated that B cells and T cells were required for anti-nRNP antibody synthesis. As expected, helper function for antibody synthesis by autologous B cells resided in the T4-cell population and suppressor function in the T8-cell population. T8 cells from SLE patients with anti-nRNP antibody alone suppressed anti-nRNP antibody synthesis by autologous B cells irrespective of clinical activity. This is in contrast to anti-dsDNA antibody production, which was not suppressed by autologous T8 cells. These results indicate that the cellular regulation of anti-nRNP antibody synthesis in SLE is different from that of anti-dsDNA antibody synthesis. Increased anti-nRNP antibody synthesis may be due to increased T4-helper cell function rather than defective T8-suppressor function.

Adult↗

PubMed1988

Suppression of in vitro production of anti-U1-ribonucleoprotein antibody by monoclonal anti-idiotypic antibody to anti-U1-ribonucleoprotein antibody.

We produced monoclonal anti-idiotypic antibody against immunoaffinity purified anti-U1-ribonucleoprotein (RNP) antibody from a patient (K.T.), by the cell fusion procedure. The specificity of monoclonal anti-idiotypic antibody (IgG1, kappa) was determined by inhibition studies. With the monoclonal anti-idiotypic antibody, cross-reactive idiotypes on anti-U1-RNP antibodies from unrelated patients with anti-U1-RNP antibody was detected in 57% of the samples. The anti-idiotypic antibody specifically suppressed the in vitro production of anti-U1-RNP antibody by lymphocytes from the patient K.T., and unrelated patients with a cross-reactive idiotype, in whom idiotype-reactive T cells were demonstrated. The results indicate that anti-idiotypic antibody may modulate the regulation of in vitro anti-U1-RNP antibody production.

Animals↗

PubMed1988

Serological and clinical study of herpes simplex virus infection in patients with sudden deafness.

A serosurvey for antibodies against type 1 and type 2 herpes simplex virus (HSV) was performed in consecutive sera collected from 61 patients with sudden deafness. A positive test for neutralizing antibody to type 1 HSV was found in 80% of patients and 77% of controls, a non-significant value. Almost all the patients possessing neutralizing antibody had complement-fixing antibody too, which some controls would have lost in the course of time. The kinetic survey of the antibody titers during the clinical course demonstrated constant levels of these antibodies. It is suggested that there may be some relationship of HSV to sudden deafness and that reactivation of a latent infection may play an important role in the etiology of this disease. We found some relationship between the serological data and the clinical findings with respect to hearing recovery.

Adolescent↗

PubMed1988

Morphological changes in the cochlear aqueduct following herpes simplex virus inoculation into the subarachnoid space.

Type 1 herpes simplex virus (HSV-1) was inoculated into the subarachnoid space through the cisterna magna of guinea pigs to study morphological changes of the inner ear and the ability of the cochlear aqueduct to protect the inner ear. Although most of the animals developed clinical manifestations of meningoencephalitis within a few days after inoculation, Preyer's reflex remained intact. Scanning electron microscopy revealed some significant changes in the cochlear aqueduct. Lymphocytes and macrophages were predominant, with narrowing of reticular tissue spaces caused by the swelling of the periotic duct tissue. The cribriform structure of the internal orifice of the cochlear aqueduct appeared to be completely obstructed, whereas it was normal in the presence of bacterial infection as previously reported (1). The morphological changes were confined to the cochlear aqueduct.

Animals↗

PubMed1987

Defects of autologous mixed lymphocyte reaction-activated immunoregulatory T cells in patients with systemic lupus erythematosus.

The present study was undertaken to determine the nature of the immunoregulatory T-cell defect after autologous mixed lymphocyte reaction (AMLR) activation in patients with systemic lupus erythematosus (SLE). Although AMLR was decreased in patients with SLE compared with normals, there was no difference in major proliferative cells (T4 cells and T4+JRA+ subset) in response to AMLR. Functional activity of AMLR-stimulated T4 subsets in patients with SLE and normals was examined in helper and suppressor/inducer assay, using pokeweed mitogen (PWM)-driven IgG synthesis. The T4+JRA- (helper) subset from SLE patients showed no greater activity than normals. However the T4+JRA+ (suppressor/inducer) subset from SLE patients showed decreased suppression induction compared with normals. This defect in the suppressor/inducer function was demonstrated even in patients with inactive SLR or in remission.

Adult↗

PubMed1987

T cell regulatory disturbances in the rheumatic diseases.

Significant immunoregulatory abnormalities have been described in both SLE and RA. In SLE, deficient suppressor T cell activity may result from depletion of CD8+ suppressor precursors, depletion of CD4+ suppressor-inducer cells, or impaired lymphokine production and deficient CD4+ cell activation of suppression by CD4+ cells. The net result is an apparent failure to inhibit antibody synthesis. The defects in RA are less well defined, although in RA there also is evidence that either deficient suppression or deficient suppression-induction plays a role in the pathogenesis of disease. There is evidence for local lymphocyte activation in the synovium, with possibly impaired local immunoregulation. However, the precise nature of the immune reactions in the synovium and their relationship to systemic immunoregulatory abnormalities remain unclear.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1987

Acute bilateral deafness with nephritis: a human temporal bone study.

Temporal bone pathology is described in a 37-year-old man who had acute, bilateral, profound sensorineural hearing loss without improvement 4 months before death. The patient had suffered from low complement nephritis, for which he had received prednisolone therapy. Autopsy revealed malignant lymphoma with non-Hodgkin's type, membranous proliferative glomerulonephritis and necrotizing vasculitis of middle and small arteries. In the temporal bone study, pathological changes were limited to the cochlear region. The vestibular structure showed no detectable pathological changes. The changes included total absence of the organ of Corti, atrophy and/or disappearance of the stria vascularis in the upper turns, collapse of Reissner's membrane in the middle turn, and new bone formation in the apical turn.

Adult↗