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Biomedical subjects

K Nohara

Publications and source records attributed to K Nohara.

At least 19 recordsLinked to original sources
PubMed2002

Effect of a single oral dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin on immune function in male NC/Nga mice.

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces immunosuppression in humans and animals. However, the effect of TCDD on Th2-type immune responses such as allergic reactions has been unclear. Using NC/Nga mice that developed atopic dermatitis-like skin lesions with marked elevation in plasma of total IgE when bred under conventional conditions, we investigated the effects of a single oral dose of TCDD on immune responses. NC/Nga mice received a single oral dose (0 or 20 microg/kg body weight) of TCDD. On day 7, treatment with TCDD alone decreased the cellularity of thymus. However, treatment with TCDD modified the cellularity of spleens and mesenteric lymph nodes (MLNs) but not of the thymus on day 28. When NC/Nga mice received ip immunization with OVA and alum on the same day as the TCDD treatment (0, 5, or 20 microg/kg body weight), TCDD markedly suppressed the concentrations of Th2-type cytokines (e.g., IL-4 and IL-5) in culture supernatants of spleen cells, whereas IFN-gamma production significantly increased. TCDD exposure reduced anti-OVA and total IgE antibody titers in plasma and did not induce the development of atopic dermatitis-like lesions in the pinnae or dorsal skin of NC/Nga mice. These results suggest that in NC/Nga mice, exposure to TCDD may impair the induction of Th2-type immune responses.

Administration, Oral↗
PubMed2001

Induction of the imbalance of helper T-cell functions in mice exposed to diesel exhaust.

Administration of diesel exhaust particles (DEP) increases antigen-specific IgE production and IgE-secreting cells, and induces Th2-type cytokine profiles in the airway in mice and humans. To determine the early effects of diesel exhaust (DE) inhalation on the cytokine production profile, BALB/c mice were exposed to 0 (controls) and 1.0 mg/m3 DE inhalation for 4 weeks. Intraperitoneal sensitization with ovalbumin (OVA) was conducted immediately before DE inhalation. Mice were treated with anti-CD4 or anti-CD8 mAb 1 day before and after the sensitization. On day 21, these mice were boosted with OVA and blood; bronchoalveolar lavage (BAL) fluid, and spleens were collected on day 28. In BAL fluid, both TNFalpha and IL-10 production in DE-exposed and control mice remained basically the same. IL-6 production in the anti-CD4 treatment group of DE-exposed mice, however, significantly increased compared with that of the controls. In vitro antigen-stimulated interleukin-4 (IL-4) and -10 (IL-10) production in spleen cells of exposed mice were not affected by low-dose DE inhalation. In vitro interferon (IFN)-gamma production in the anti-CD4 treated group of exposed mice decreased markedly. Although anti-OVA IgE production in the plasma of sham-treated mice exposed to DE was the same level as for controls, anti-CD4 mAb treatment in DE-exposed mice significantly reduced IgE production compared to controls. In anti-OVA IgG1 production, anti-CD4 or anti-CD8 mAb treatment in DE-exposed groups also significantly reduced. Anti-OVA IgG2a production was reduced by treatment with anti-CD4 mAb, but increased by anti-CD8 mAb treatment in DE-exposed mice. Low dose DE inhalation is thus shown to adversely affect the cytokine and antibody production in mice by altering CD4+ and CD8+ T-cell functions.

Administration, Inhalation↗
PubMed2001

Cl atom-initiated oxidation of three homologous methyl perfluoroalkyl ethers.

Chlorine atom-initiated photooxidations of three homologous methyl perfluoroalkyl ethers (HFEs), n-C(n)F(2n+1)OCH3 (n = 2, 3, and 5), in air in the absence of NOx were investigated with a long path FTIR/photochemical reaction system to elucidate the degradation mechanisms. The environmental removal processes of these three ethers in the troposphere were estimated. For oxidation of the three ethers, perfluoroalkyl formates (C(n)F(2n+1)OCHO; n = 2, 3 and 5) as relatively stable intermediates were produced at unity of the production ratio, which was independent of the perfluoroalkyl length. The rate constants for the reaction of Cl atoms with C2F5OCHO, C3F7OCHO, and C5F11OCHO were (1.2 +/- 0.5) x 10(-14), (1.2 +/- 0.5) x 10(-14), and (1.8 +/- 0.7) x 10(-14) cm3 molecule(-1) s(-1), respectively. The rate constants of the reaction of Cl with produced perfluoroalkyl formates were larger than these of perfluoroalkyl ethers. The formyl group of the perfluoroalkyl formates was finally converted to carbon dioxide. The -CF2- of the perfluoroalkyl groups for the three ethers was mainly converted to COF2 through the C-C cleavage; the conversion ratios from the carbons of the perfluoroalkyl group to COF2 were 48 +/- 10, 76 +/- 10, and 60 +/- 10% for C2F5OCH3, n-C3F7OCH3, and n-C5F11OCH3, respectively. Sixteen percent of the perfluoroalkyl group for n-C3F7OCH3 was converted to C2F5COF. Similarly, the perfluoroalkyl group of n-C5F11OCH3 was converted to C(n)F(2n+1)COF (n = 2, 3, and/or 4) with the yield of 15-30%, while for C2F5OCH3, the formation of CF3COF was not confirmed. As an oxidation product of the terminal CF3- group, 20, 22, and 16% of the CF3 group for C2F5OCH3, n-C3F7OCH3, and n-C5F11OCH3, respectively, were converted to CF3OOOCF3.

Biodegradation, Environmental↗
PubMed2001

Roles of CD4+ and CD8+ T cells in adjuvant activity of diesel exhaust particles in mice.

Through an imbalance in Th1 and Th2 cytokine profiles, diesel exhaust particles (DEP) are thought to induce Th2-dominated IgE and IgG1 production. However, the roles of CD4+ and CD8+ T-cell subtypes in the increased immune responses to antigen in mice exposed to DEP are unclear. In the present study, we investigated whether treatment with anti-CD4 or anti-CD8 mAb abrogated the adjuvant activity of DEP. On day -1 and day 1, each group of mice was injected intraperitoneally with anti-CD4, anti-CD8, or rat IgG (vehicle). On day 0, the mice were immunized with ovalbumin (OVA) or OVA plus DEP. After 3 weeks, each mouse was boosted with 10 microg of OVA alone. On day 7 after the first injection with OVA+DEP or OVA alone, the numbers of total, IA+, CD80+/IA+ and CD86+/IA+ cells in peritoneal exudate cells (PEC) were higher in OVA+DEP-immunized mice than in OVA-immunized mice. Depletion of CD8+ cells resulted in a modulation of the production of granulocyte-macrophage colony-stimulating factor, IL-12 and PGE(2) in peritoneal exudate fluid from OVA+DEP-immunized mice. On day 28, DEP injection markedly increased IL-4 production in the culture supernatants of spleen cells from CD4+ or CD8+-depleted mice. Depletion of CD8+ cells in OVA+DEP-immunized mice resulted in a decrease in IFN-gamma production compared with that in OVA-immunized mice. Adjuvant activity of DEP was observed in anti-OVA IgE, anti-OVA IgG1, anti-OVA IgG3, and total IgE production. Depletion of CD4+ T cells abrogated the adjuvant effect of DEP on anti-OVA IgE, and anti-OVA IgG1 production in plasma. However, depletion of CD8+ T cell inhibited the upregulated anti-OVA IgG3 production. These findings suggest that DEP injection may affect not only the function of CD4+ cells but also that of CD8+ T-cell subsets to modulate the synthesis of proinflammatory cytokine in PEC and type-1 and type-2 cytokine production in spleens.

Adjuvants, Immunologic↗
PubMed2001

Change in levator veli palatini muscle activity of normal speakers in association with elevation of the velum using an experimental palatal lift prosthesis.

OBJECTIVE: The purpose of this study was to examine whether mechanical elevation of the velum can directly affect the levator veli palatini muscle (LVP) activity using normal speakers as subjects. DESIGN: Each subject was instructed to produce /mu/, /u/, /pu/, /su/, and /tsu/ in a speech task and to blow with maximum possible effort. Smoothed electromyographic activity of the LVP was recorded with an experimental palatal lift prosthesis (PLP) both in place and removed. PARTICIPANTS: Four normal speakers were used as subjects. RESULTS: LVP activity for all tasks was significantly smaller (p <.001; Student's t test) with the PLP in place than without the PLP for all subjects. An analysis of variance (p <.001) clarified that activity ranges of the LVP were significantly different between the removal and placement conditions for all the subjects. CONCLUSION: The result was similar to that previously obtained for patients with velopharyngeal incompetence wearing a PLP. It is possible that the decrease in the LVP activity in association with placement of a PLP is caused by the direct effect of mechanical elevation, which decreases the distance the velopharyngeal mechanisms must travel for complete closure of the velopharynx.

Adult↗
PubMed2000

The effects of perinatal exposure to low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin on immune organs in rats.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is revealed to exert diverse biological effects including immunotoxicity, mainly by inadvertently activating the transcription factor arylhydrocarbon receptor (AhR). In the present study, the developmental effects of perinatal exposure to low doses of TCDD on the major immune organs of offspring, thymus and spleen, were investigated focusing on weaning time (postnatal day (PND) 21), puberty (PND 49) and adulthood (PND 120) in male rats. Concurrently, TCDD contents in those organs were measured with a high-resolution gas chromatography-mass spectrometry (GC/MS). In the thymus and spleen, CYP1A1 mRNA induction, the sensitive reaction caused by activation of AhR, was also measured in order to examine whether perinatally administered TCDD can elicit gene expressions in these organs. When pregnant dams were administered a single oral dose of 12.5-800 ng TCDD/kg body weight on gestation day (GD) 15, the weights of the thymus and spleen of the offspring did not differ from those of control animals throughout the experiments. The thymus and spleen maternally exposed to 800 ng TCDD/kg contained 102.0 and 62.7 pg TCDD/g tissue on PND 21, respectively, and the amounts decreased thereafter. In the thymus, dose-dependent CYP1A1 mRNA induction was clearly observed by maternal exposure to 50-800 ng TCDD/kg on PND 5. The induction was gradually decreased on PND 21 and 49. On the other hand, CYP1A1 mRNA induction in the spleen was very weak. In these thymi, no reproducible change was observed by TCDD exposure in cell number and cellular population defined by CD4 and CD8 molecules at any time. In contrast, splenocyte number was shown to decrease by maternal exposure to 12.5-800 ng TCDD/kg in a dose-dependent manner on PND 49. The alteration in spleen cellularity by TCDD was not detected on PND 21 or 120. These results clarified that perinatal exposure to low doses of TCDD affects the immune organs, which is apparent in spleen around puberty and likely to be hardly relevant to AhR-dependent gene expressions.

Animals↗
PubMed2000

Induction of apoptosis in mouse thymocytes by cadmium.

In the thymus apoptosis is an important process in T cell maturation and differentiation. Cadmium (Cd) is an ubiquitous toxic metal that is capable of modulating immune responses. To investigate the induction of apoptosis and immunomodulation by environmental chemicals, we cultured mouse thymocytes with Cd and/or dexamethasone (DEX). DNA fragmentation was analyzed by gel electrophoresis, ELISA and flow cytometry. Treatment with either Cd or DEX induced DNA fragmentation in the thymocytes. Exposure to 10 microM Cd killed thymocytes by apoptosis rather than necrosis. However, no synergistic or additive effect was observed in the induction of apoptosis when DEX was added to the Cd. These results suggest that Cd may modulate the function of the thymus by the induction of apoptosis through mechanisms that differ from those used by DEX.

Animals↗
PubMed2000

Alterations of thymocyte development, thymic emigrants and peripheral T cell population in rats exposed to 2,3,7, 8-tetrachlorodibenzo-p-dioxin.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exerts diverse biological effects by activating the cytosolic transcription factor, arylhydrocarbon receptor (AhR), which translocates to nuclei by TCDD binding and induces gene expressions. Among the well known-adverse effects of TCDD is thymus atrophy. In thymus atrophy, TCDD alters the proliferation as well as the differentiation of immature thymocytes. Previous studies on the effects of TCDD on thymocyte development were primarily carried out with high doses of TCDD. The present study investigates the effects of lower doses of TCDD (1 or 2 microg TCDD/kg by gavage) on thymocyte development, and furthermore, their sequential consequences on the peripheral T cell repertoire. Seven days after treatment with 1 or 2 microg TCDD/kg, the expression of CYP1A1 mRNA, one of the sensitive responses caused by the binding of TCDD to AhR, was detected in the thymus of rats. Thymus weights and thymus cell numbers decreased in TCDD-treated rats in a dose-dependent manner. The ratios of CD4 single-positive (SP) cells/CD8 SP cells were significantly reduced by TCDD exposure, indicating that the maturation of CD4(+)CD8(+) double-positive (DP) cells was skewed toward CD8 SP cells. These changes in the thymus were parallel to those previously observed with high doses of TCDD exposure. However, the specific reduction of DP cells reported in previous studies with high doses of TCDD was not detected in the present study. On the other hand, the skewing of mature CD4/CD8 T cell ratio in thymocytes by TCDD was not reflected in mesenteric lymph node (LN) lymphocytes, where the proportion of CD8 T cells was rather lowered by TCDD with a significant difference at 1 microg TCDD/kg. In LN lymphocytes, the percentage of recent thymic emigrants (RTEs), defined by the surface markers of Thy1(+)CD45RC(-), was shown to be significantly reduced by exposure to 1 and 2 microg TCDD/kg. T cell supply from the thymus has a crucial role in keeping the diversity of the T cell repertoire. The results of the present study indicated that lower doses of TCDD affect thymocyte development, especially differentiation, and reduce the proportion of RTE in LN, which may cause immunosuppression by reducing the variety of the T cell receptor repertoire.

Animals↗
PubMed2000

Effect of placement of a speech appliance on levator veli palatini muscle activity during speech.

OBJECTIVE: The purposes of this electromyographic study were to examine whether levator veli palatini muscle activity during speech can be changed with placement of a speech appliance and to clarify whether or not the change is related to the type of speech appliance used. DESIGN: Electromyography (EMG) was performed during production of speech samples in two conditions: with placement and with removal of a speech appliance. Speech samples were the vowel /omega/ and consonant-vowel (omega) syllables, including nasal, plosive, fricative, and affricate consonants. SETTING: Division for Oral-Facial Disorders, Faculty of Dentistry, Osaka University Dental Hospital, Japan. PARTICIPANTS: Subjects were six patients with repaired cleft palate and velopharyngeal inadequacy (VPI); three routinely wore a palatal lift prosthesis to correct borderline VPI, and the other three wore a speech appliance hybrid that consisted of a pharyngeal bulb and a palatal lift. INTERVENTIONS: Each patient was asked to produce each speech sample in both conditions of placement and removal of their respective appliances. MAIN OUTCOME MEASURES: Smoothed EMG signals of the levator veli palatini muscle were recorded with and without the appliance during five repetitions of each speech sample. The average value of peak smoothed levator EMG was compared between placement and removal conditions for all subjects and between the two subject groups in each experimental condition. RESULTS: With a speech appliance in place, the range of levator activity was distributed in a portion lower than that in the removed condition for subjects in both appliance groups. In addition, the intervals were smaller in the placement condition than in the removed condition. CONCLUSION: A speech appliance may prevent hypernasality, nasal emission of air, or both associated with VPI because of mechanical obturation of the velopharynx and an alteration in velopharyngeal function.

Adolescent↗
PubMed1999

Effect of environmental pollutants on the production of pro-inflammatory cytokines by normal human dermal keratinocytes.

The effect of the environmental pollutants, diesel exhaust particles (DEP) and formaldehyde (FA), on the production of pro-inflammatory cytokines (interleukin (IL)-1alpha, IL-1beta, tumor necrosis factor (TNF)-alpha and IL-8) by normal human dermal keratinocytes (hKCs) was investigated. Normal hKCs were incubated with various concentrations of DEP (0.4, 0.8, 4, or 20 microg/ml) or FA (0.25, 0.5, 1, or 5 microg/ml), and cytokine production was then determined by enzyme-linked immunosorbent assay (ELISA). DEP (20 microg/ml) induced IL-1beta production without altering cell growth. The increased production of IL-1beta induced by this concentration of DEP was further enhanced by the presence of phorbol 12-myristate 13-acetate (PMA), although PMA alone did not affect the levels of IL-1beta. IL-8 production was also increased by DEP (0.4 and 0.8 microg/ml), which is consistent with the results that these concentrations of DEP increased the number of cells significantly after 72 h incubation. Although FA alone did not stimulate the production of IL-1beta or IL-8 by keratinocytes, FA (0.5 microg/ml and 5 microg/ml) significantly increased IL-8 and IL-1beta production, respectively, in cells stimulated with PMA. IL-1alpha production was not modulated by FA or DEP even in the presence of PMA. TNF-alpha was produced by unstimulated keratinocytes at barely detectable levels after 48 h incubation. Although basal levels of TNF-alpha in the culture supernatants were increased after stimulation with PMA, neither pollutant alone nor combination with PMA affected the levels of TNF-alpha. These in vitro findings suggest that environmental pollutants may act as modulating factors of cutaneous inflammation by affecting the ability of keratinocytes to release pro-inflammatory cytokines.

Cells, Cultured↗
PubMed1999

Involvement of focal adhesion kinase in inhibition of motility of human breast cancer cells by sphingosine 1-phosphate.

Sphingosine 1-phosphate (SPP), a bioactive sphingolipid metabolite, inhibits chemoinvasiveness of the aggressive, estrogen-independent MDA-MB-231 human breast cancer cell line. As in many other cell types, SPP stimulated proliferation of MDA-MB-231 cells, albeit to a lesser extent. Treatment of MDA-MB-231 cells with SPP had no significant effect on their adhesiveness to Matrigel, and only high concentrations of SPP partially inhibited matrix metalloproteinase-2 activation induced by Con A. However, SPP at a concentration that strongly inhibited invasiveness also markedly reduced chemotactic motility. To investigate the molecular mechanisms by which SPP interferes with cell motility, we examined tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin, which are important for organization of focal adhesions and cell motility. SPP rapidly increased tyrosine phosphorylation of FAK and paxillin and of the paxillin-associated protein Crk. Overexpression of FAK and kinase-defective FAK in MDA-MB-231 cells resulted in a slight increase in motility without affecting the inhibitory effect of SPP, whereas expression of FAK with a mutation of the major autophosphorylation site (F397) abolished the inhibitory effect of SPP on cell motility. In contrast, the phosphoinositide 3'-kinase inhibitor, wortmannin, inhibited chemotactic motility in both vector and FAK-F397-transfected cells. Our results suggest that autophosphorylation of FAK on Y397 may play an important role in SPP signaling leading to decreased cell motility.

Breast Neoplasms↗
PubMed1999

Effect of placement of a speech appliance on levator veli palatini muscle activity during blowing.

OBJECTIVE: We have observed clinically that some speakers wearing a speech appliance for correction of velopharyngeal incompetence can blow with variable intensity without nasal air escape. This clinical finding suggests that tightness of velopharyngeal closure may be regulated in accordance with oral air pressure during blowing. The purposes of this electromyographic study were (1) to examine whether levator vell palatini muscle activity can be changed in relation to oral air pressure during blowing when the speech appliance is removed, (2) to clarify whether or not the change is related to the severity of velopharyngeal incompetence, and (3) to examine whether placement of a speech appliance can alter levator muscle activity into the equivalent of that of normal speakers during blowing. DESIGN: Eight patients with repaired cleft palate, who routinely wear a palatal lift prosthesis (PLP) or a hybrid speech appliance of a pharyngeal bulb and palatal lift (bulb-PLP), served as subjects. Subjects were classified into one of two groups according to their speech appliance (PLP group and bulb-PLP group). Electromyography of the levator veli palatini muscle was recorded with a speech appliance in place and then with the speech appliance removed as the subject blew through a tube at three different effort levels. RESULTS: In the removed condition, the change in levator activity in relation to oral air pressure was variable across subjects in the bulb-PLP group, whereas levator activity changed in relation to oral air pressure change for all subjects in the PLP group. However, levator activity changed in relation to oral air pressure with either speech appliance in place for all subjects irrespective of their speech appliance types. CONCLUSION: The severity of velopharyngeal incompetence might be related in part to change in levator activity in association with oral air pressure. The effect of a speech appliance to correct velopharyngeal incompetence might consist not only of mechanical obturation of the velopharynx but also of alteration of velopharyngeal function to become similar to normal speakers. Moreover, it is likely that the velopharyngeal system could be well regulated so as to exhibit a consistent outcome of velopharyngeal function.

Adolescent↗
PubMed1998

Glycosphingolipid composition of MDA-MB-231 and MCF-7 human breast cancer cell lines.

Much evidence has shown that glycosphingolipids are involved in cellular recognition, regulation of cell growth, and metastasis. In the present study, the major glycosphingolipids of two widely studied human breast cancer cell lines were examined. The MCF-7 cell line has functional estrogen and EGF receptors, is dependent on estrogen and EGF for growth, and is uninvasive, while MDA-MB-231 cells are a model for more aggressive, hormone-independent breast cancer. There was twice as much neutral glycolipid in MCF-7 cells as in MDA-MB-231 cells. The major neutral glycolipids in MDA-MB-231 cells were identified as CTH and globoside. MCF-7 cells also contained as the major neutral glycolipids CTH as well as globoside and two other glycolipids which were tentatively identified as galactosylgloboside and fucosylgalactosylgloboside by exoglycosidase treatments. Conversely, the ganglioside content was four fold higher in MDA-MB-231 cells compared to MCF-7 cells. The abundant gangliosides in both cell lines were GM3, GM2, GM1, and GD1a. A minor monosialoganglioside was detected in MDA-MB-231 cells. The striking 18 fold greater amount of GM3 in MDA-MB-231 cells may have important implications because GM3 has been suggested to be involved in regulation of growth factor functions. In agreement, insertion of ganglioside GM3 into the plasma membrane of MCF-7 cells blocked the growth stimulatory effect of EGF.

Breast Neoplasms↗
PubMed1998

Renal involvement in Henoch-Schönlein purpura: a multivariate analysis of prognostic factors.

This study is the first report in which the relationship between the progression of renal involvement in Henoch-Schönlein purpura (HSP) and various factors was evaluated using a multivariate analysis. Sixty-five (33.5%) of 194 patients with HSP developed renal involvement from three days to 17 months after the onset of the disease. The plasma coagulation factor XIII (F XIII) activity of 97 patients was examined, and 51 (54.3%) of them showed a decreased activity. A univariate analysis showed that an age at the onset of more than seven years, persistent purpura and a decreased F XIII activity all increased the risk of developing renal involvement. A Cox regression model analysis indicated severe abdominal symptoms, persistent purpura and decreased F XIII activity to be significant risk factors and their hazard ratios were 3.26, 11.53 and 2.27, respectively. Corticosteroid treatment had a hazard ratio of 0.36 and was considered to decrease the risk of developing renal involvement. Based on these findings, patients who have the risk factors for renal involvement should be treated with corticosteroids at the onset of the disease to prevent developing renal involvement.

Adolescent↗
PubMed1998

Antibody against ganglioside GD1c containing NeuGcalpha2-8NeuGc cooperates with CD3 and CD4 in rat T cell activation.

Gangliosides have long been implicated in T cell activation. GD1c with two N-glycolylneuraminic acids [GD1c(NeuGc,NeuGc)] is the predominant ganglioside in rat T cells. In the present study, the anti-GD1c(NeuGc,NeuGc) mAb, AC1, which binds to the NeuGcalpha2-8NeuGcalpha2- sequence, was found to enhance Con A-activated cellular proliferation at a concentration at which AC1 alone did not activate the cells. The potentiation by AC1 was observed more consistently and effectively in the cellular activation elicited by cross-linking of anti-CD3 and anti-CD4, rather than in the cell growth induced by immobilized anti-CD3 alone. Moreover, the combination of immobilized anti-CD4 and soluble AC1 had a remarkable mitogenic effect. In addition, we have demonstrated the existence of a 100 kDa protein in rat T cell lysates which reacts with AC1 on Western blots, and this interaction is abolished by sialidase-treatment of the membrane. Pronase treatment of the T cells, which rendered the 100 kDa protein undetectable on Western-blotting, reduced the number of AC1-positive cells by 40-50% on flow cytometry. On the other hand, all cells became AC1-negative after sialidase treatment. These findings indicated that AC1 reacts with both GD1c(NeuGc,NeuGc) and the 100 kDa glycoprotein on rat T cells. Taken together, these results predict the presence of a novel regulatory mechanism of T cell activation involving CD4 and the NeuGcalpha2-8NeuGcalpha2- sequence.

Animals↗
PubMed1997

Gangliosides involved in activation of rat T lineage cells.

Gangliosides have long been known to be involved in T-cell activation. In our previous studies, a unique GMlb-derived ganglioside, GD1c(NeuGc,NeuGc), was shown to be the predominant ganglioside in rat thymocytes and T-cells. Upon the activation of the thymocytes, the amount of GD1c(NeuGc,NeuGc) increases remarkably, and additionally a novel species of GD1b, GD1b(NeuGc,NeuGc), appears as the other major ganglioside (Nohara, et al. (1993) J. Biol. Chem. 268, 24997-25000). In the present study, monoclonal antibodies (MAbs) against these two gangliosides have been generated. The MAb AC1 established by immunizing mice with purified GD1c(NeuGc,NeuGc) reacted strongly with GD1c(NeuGc,NeuGc) and weakly with GD1b(NeuGc,NeuGc) by enzyme-linked immunosorbent assay (ELISA). The other MAb AB1 obtained by immunization with GD1b(NeuGc,NeuGc) showed a strong binding activity to GD1b(NeuGc,NeuGc) and no reactivity to GDlc(NeuGc,NeuGc) by ELISA. Flow cytometry analyses using these MAbs have revealed that an AC1-positive subset exists in a portion of resting CD4+CD8- thymocytes and CD4+ splenic T-cells. When the thymocytes were activated with 12-O-tetradecanoylpholbol-13-acetate (TPA) and calcium ionophore A23187, the proportion of AC1+ cells increased remarkably and were detected not only in CD4+ cells but also in CD8+ cells. An increase in the proportion of AC1+ cells was also seen in activated T-cells. In contrast, AB1-positive cells were only detected in activated thymocytes, not in resting thymocytes, or resting or activated T-cells. These results implicate GD1c(NeuGc,NeuGc) in the activation of thymocytes as well as T-cells, whereas GD1b(NeuGc,NeuGc) appears to be specifically related to the activation of thymocytes.

Animals↗