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T Hiroi

Publications and source records attributed to T Hiroi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Survival and viral load in four groups of HIV-1 infected hemophiliacs compared by three-way data clustering.

We assigned a total of 131 hemophiliacs infected with HIV-1 into four clusters by applying a 3-way data analysis method. Sequentially acquired CD4+ and CD8+ cell counts obtained longitudinally over an observation period from 1986 to 1992 were analyzed. During the successive observation in this interval, a clustering of patients is not always coincident over all the times, because the cell counts vary with time. Therefore, the 3-way data clustering is to obtain the optimal result of the classification of patients through all the interval of observation. Examining patients' survival after that period, the cumulative mortality rate was highest among the 36 hemophiliacs in Cluster 1. Less mortality was found in Cluster 2, consisting of 49 hemophiliacs and none was reported in Clusters 3 and 4, which included 33 and 13 hemophiliacs, respectively. However, a significantly lower blood viral copy number was found in Cluster 3 than in Cluster 4. A total of six long-term non-progressors was found, five in Cluster 3 and one in Cluster 4, while none was found in Cluster 1 or 2. As demonstrated in this analysis, 3-way data clustering may represent a good data mining technique for handling various types of clinical data.

CD4 Lymphocyte Count↗
PubMed2000

CYP4B1 is a possible risk factor for bladder cancer in humans.

In experimental animals such as rats and rabbits, CYP4B1 has an important role in mutagenic activation of procarcinogens in bladders. In human bladders, it is not clear whether CYP4B1 has such role or not. In the present study, human bladder microsomes activated 2-aminofluorene which is a typical substrate for CYP4B1 and is a bladder carcinogen. CYP4B1 was detected in the human bladder microsomes by immunoblotting. Furthermore, we developed a microassay for CYP4B1 mRNA by performing real-time RT-PCR. Using this method, CYP4B1 mRNA levels were assayed in transurethal resection samples from the bladders of patients with bladder tumors. The bladder-tumor patients had a significantly higher expression of CYP4B1 than the nonbladder tumor patients. These findings suggest that a high expression of CYP4B1 increases the risk of bladder tumor by activation of carcinogenic aromatic amines. This approach could be an important tool in the assessment of human bladder cancer risk.

Adult↗
PubMed2000

IL-15 and IL-15 receptor selectively regulate differentiation of common mucosal immune system-independent B-1 cells for IgA responses.

We show in this report a new regulatory role for IL-15 and IL-15R in the development of B-1 cells and their differentiation into IgA-producing cells. Mucosal IgA levels were found to be inhibited by anti-IL-15 mAb treatment in vivo, but enhanced by administration of rIL-15, while serum IgA levels remained unaffected. Mucosal B-1 cells preferentially proliferated in response to IL-15 in vitro. When mucosal B-1 and B-2 cells were separated into surface (s)IgM(+)sIgA(-) and sIgM(-)sIgA(+) fractions, IL-15R-specific mRNA was found to be predominant in both sIgM(+)sIgA(-) and sIgM(-)sIgA(+) B-1 cells at a much higher level than B-2 cells. Further, incubation of these different subsets of B-1 and B-2 cells with IL-15 resulted in greater enhancement of the corresponding receptor expression by B-1 subset when compared with B-2 fraction. Interestingly, de novo isolated sIgM(+)sIgA(-) B-1, but not sIgM(+)sIgA(-) B-2, cells were already class-switched cells because the germline Calpha transcript was detected and was then further enhanced by IL-15. IL-15 also supported differentiation of both sIgM(+)sIgA(-) and sIgM(-)sIgA(+) B-1 cells into IgA-producing cells. Taken together, these findings suggest that IL-15 is a critically important cytokine for the differentiation of both sIgM(+),IgA(-) and sIgM(-)sIgA(+) B-1 cells expressing IL-15R into IgA-producing cells in mucosal tissues.

Animals↗
PubMed2000

The decreased in vivo clearance of CYP2D6 substrates by CYP2D6*10 might be caused not only by the low-expression but also by low affinity of CYP2D6.

CYP2D6 exhibits genetic polymorphism with interindividual differences in metabolic activity. We have found a significant influence on the pharmacokinetics of venlafaxine by the CYP2D6*10 allele in a Japanese population. CYP2D6.10, which is translated from CYP2D6*10, has two amino acid substitutions: Pro34 --> Ser and Ser486 --> Thr. In this study, CYP2D6.10 was expressed in Saccharomyces cerevisiae and its catalytic activity for CYP2D6 substrates was investigated. The CYP2D6*10B- and *10C-associated cDNA were isolated from human lymphocyte genotyped as CYP2D6*10. In addition, three forms of CYP2D6, Pro34/Thr486 (PT), Ser34/Ser486 (SS), and Pro34/Ser486 (wild type, CYP2D6.1), were constructed by PCR-site mutagenesis to clarify the effects of the two amino-acid substitutions. The expression of CYP2D6 protein was confirmed by immunoblotting using CYP2D antibody. The absorbance at 450 nm was measured by CO-reduced difference spectra from five all microsome preparations. The CYP2D6 forms with Pro34 --> Ser amino acid substitution were at a lower expression than CYP2D6.1 from the findings of immunoblotting and spectral analysis. The apparent K(m) values of CYP2D6.1, CYP2D6.10A, and CYP2D6.10C were 1.7, 8.5, and 49.7 microM, respectively, for bufuralol 1'-hydroxylation, and 9.0, 51.9, and 117.4 microM, respectively, for venlafaxine O-demethylation, respectively. The V(max) values were not significantly different among the three variants. These findings suggest that the decreased in vivo clearance by CYP2D6*10 was caused not only by low expression of but also the increased K(m) value of CYP2D6.

Alleles↗
PubMed2000

Area under the plasma concentration-time curve of inorganic fluoride following sevoflurane anesthesia correlates with CYP2E1 mRNA level in mononuclear cells.

BACKGROUND: Because the amount of inorganic fluoride released after anesthesia with sevoflurane depends on the dose of administered sevoflurane and cytochrome P450 (CYP) 2E1 activity in the liver, a reliable and noninvasive probe for CYP2E1 would be useful for predicting plasma inorganic fluoride levels after anesthesia. In this study, the authors evaluated the relation between plasma concentration of inorganic fluoride after sevoflurane anesthesia and CYP2E1 mRNA level in mononuclear cells. METHODS: Twenty patients (American Society of Anesthesiologists physical status I), aged 20-68 yr undergoing body surface surgery with general anesthesia with sevoflurane were enrolled. One milliliter of blood was obtained before administration of sevoflurane and mononuclear cells were obtained. Levels of CYP2E1 mRNA in mononuclear cells were measured by competitive reverse transcription polymerase chain reaction with a specific primer and competitor for CYP2E1 mRNA. RESULTS: There was a significant correlation between level of CYP2E1 mRNA in mononuclear cells and the area under the plasma concentration-time curve of plasma inorganic fluoride from the beginning of sevoflurane administration to infinity in uninduced and uninhibited patients (r2 = 0.56; P < 0.01). CONCLUSIONS: Area under the plasma concentration-time curve of inorganic fluoride after sevoflurane anesthesia correlates with CYP2E1 mRNA in mononuclear cells in peripheral blood.

Adult↗
PubMed2000

Unique characteristics of lacrimal glands as a part of mucosal immune network: high frequency of IgA-committed B-1 cells and NK1.1+ alphabeta T cells.

PURPOSE: Immunologic characterization of IgA-committed B-1 and B-2 cells, and unique subsets of T cells isolated from the murine lacrimal gland (LG), the primary exocrine tissue for the ocular surface, which is considered to be a part of the mucosal immune system. METHODS: Single cells were obtained from LGs of C57BL/6 mice by the enzyme dissociation method using collagenase type IV. Samples underwent flow cytometric analysis to characterize the unique subsets of T and B cells. To test the effectiveness of ocular vaccination, mice were immunized ocularly or nasally with cholera toxin (CT; 10 microg/mouse) suspended in phosphate-buffered saline. Antigen-specific immune responses were determined by isotype and CT-specific enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot (ELISPOT) assay. RESULTS: When mononuclear cells (MC) isolated from LG samples were examined by flow cytometry, approximately 28% of cells were characterized as B220+ B cells. Because surface IgA+ (sIgA+) B cells develop from B-1 and B-2 lineages, it was important to examine which subset of B cells gives rise to LG sIgA+ B cells. Examination of the MC isolated from LG samples showed that approximately 4% of cells were sIgA+ B cells. Furthermore, nearly all these sIgA+ B cells (97.5%) belonged to the B-1 lineage, especially the B-1a cell line (B220low, CD5+). Of the isolated CD3+ T cells, 75% were alpha(beta) and 25% were gamma(delta)T-cell receptor positive. The proportion of NK1.1+ alpha(beta) T cells was higher (3%) in LG samples than in submandibular gland samples (0.5%). Ocular immunization with CT-induced antigen-specific mucosal (e.g., found in tear-wash and saliva samples) and systemic (e.g., serum) immune responses. The magnitude of antigen-specific antibody responses was comparable to those induced by nasal immunization. CONCLUSIONS: These results show that LG contains unique subsets of B (e.g., sIgA+ B-1 cells) and T (e.g., NK1.1+ alpha(beta)T cells) cells. Furthermore, as a part of the mucosal immune barrier, the LG is an important immunologic tissue for the ocular surface.

Animals↗
PubMed1999

Nasopharyngeal-associated lymphoreticular tissue (NALT) immunity: fimbriae-specific Th1 and Th2 cell-regulated IgA responses for the inhibition of bacterial attachment to epithelial cells and subsequent inflammatory cytokine production.

To investigate the antibacterial activity of mucosal Th1 and Th2 immune responses induced nasally and orally, mice were immunized with mucosal vaccine containing fimbrial protein of Porphyromonas gingivalis, a causative agent for a destructive chronic inflammation in the periodontium, and cholera toxin (CT) as mucosal adjuvant. Nasal vaccine containing low doses of fimbriae (10 micrograms) and CT (1 microgram) induced Ag-specific Th1/Th2-type response in CD4+ T cells in mucosal effector tissues, including nasal passage and submandibular glands, which accounted for the generation of Ag-specific IgA-producing cells. In contrast, oral immunization required higher amounts of fimbriae and CT for the induction of Ag-specific IgA responses. Fimbriae-specific IgA mAbs generated from submandibular glands of nasally immunized mice inhibited P. gingivalis attachment to and reduced subsequent inflammatory cytokine production from epithelial cells. These findings suggest that nasal vaccination is an effective immunization regimen for the induction of Ag-specific Th1 and Th2 cell-driven IgA immune responses that possess the ability to inhibit bacterial attachment to epithelial cells and subsequent inflammatory cytokine production.

Animals↗
PubMed1999

Deficiency of IL-5 receptor alpha-chain selectively influences the development of the common mucosal immune system independent IgA-producing B-1 cell in mucosa-associated tissues.

Deletion of IL-5R alpha-chain (IL-5R alpha-/-) selectively influenced the mucosal IgA responses in vivo. While levels of IgA in mucosal secretions were more reduced in IL-5R alpha-/- mice than in wild-type mice, the levels of IgA in serum were not changed. The frequency of IgA-producing cells was reduced in mucosal effector sites (e.g., intestinal lamina propria and nasal passage), but not in inductive sites such as Payer's patches and nasal-associated lymphoreticular tissues in IL-5R alpha-/- mice. IgA-committed (surface IgA+; sIgA+) B-1 cells mainly resided in mucosal effector tissues, while conventional sIgA+ B (B-2) cells formed in mucosal inductive sites of wild-type mice. In contrast, in the effector tissue of IL-5R alpha-/- mice, sIgA+ B-1 cells, but not sIgA+ B-2 cells in the inductive site, were significantly reduced. IL-5R alpha was more expressed on sIgA+ B-1 cells than was IL-6R, while both IL-5R alpha and IL-6R were expressed on sIgA+ B-2 cells in wild-type mice. sIgA+ B-1 cells produced high levels of IgA with rIL-5 rather than of rIL-6 in vitro. Taken together, the findings suggest that the IL-5/IL-5R signaling pathway is critically important for the development of common mucosal immune system independent sIgA+ B-1 cell in mucosal effector tissues in vivo.

Animals↗
PubMed1999

Mitochondrial thioredoxin reductase in bovine adrenal cortex its purification, properties, nucleotide/amino acid sequences, and identification of selenocysteine.

Mitochondrial thioredoxin reductase was purified from bovine adrenal cortex. The enzyme is a first protein component in the mitochondrial thioredoxin-dependent peroxide reductase system. The purified reductase exhibited an apparent molecular mass of 56 kDa on SDS/PAGE, whereas the native protein was about 100 kDa, suggesting a homodimeric structure. It catalysed NADPH-dependent reduction of 5, 5'dithiobis(2-nitrobenzoic acid) and thioredoxins from various origins but not glutathione, oxidized dithiothreitol, DL-alpha-lipoic acid, or insulin. Amino acid and nucleotide sequence analyses revealed that it had a presequence composed of 21 amino acids which had features characteristic of a mitochondrial targeting signal. The amino acid sequence of the mature protein was similar to that of bovine cytosolic thioredoxin reductase (57%) and of human glutathione reductase (34%) and less similar to that of Escherichia coli (19%) or yeast (17%) enzymes. Human and bovine cytosolic thioredoxin reductase were recently identified to contain selenocysteine (Sec) as one of their amino acid constituents. We also identified Sec in the C-terminal region of mitochondrial (mt)-thioredoxin reductase by means of MS and amino acid sequence analyses of the C-terminal fragment. The four-amino acid motif, Gly-Cys-Sec-Gly, which is conserved among all Sec-containing thioredoxin reductases, probably functions as the third redox centre of the enzyme, as the mitochondrial reductase was inhibited by 1-chloro-2,4-dinitrobenzene, which was reported to modify Sec and Cys covalently. It is known that mammalian thioredoxin reductase is different from bacterial or yeast enzyme in, for example, their subunit molecular masses and domain structures. These two different types of enzymes with similar activity are suggested to have evolved convergently. Our data clearly show that mitochondria, which might have originated from symbiotic prokaryotes, contain thioredoxin reductase similar to the cytosolic enzyme and different from the bacterial one.

Adrenal Cortex↗
PubMed1999

Isoform-selective metabolism of mianserin by cytochrome P-450 2D.

The involvement of cytochrome P-450 (CYP) 2D isoforms in the metabolism of mianserin and the stereoselectivity of their catalytic activities were investigated by using five CYP2D isoforms (CYP2D1, 2D2, 2D3, 2D4, and 2D6). Using RS-mianserin as a substrate, we found that five CYP2D isoforms had similar levels of 8-hydroxylation activity. However, N-demethylation activity differed among the isoforms; CYP2D3 and 2D4 efficiently demethylated RS-mianserin compared with the other three isoforms. N-Oxidation activity was specific to CYP2D1 although its level was relatively low. Another metabolite, assigned as 8-hydroxy-N-desmethylmianserin by liquid chromatography/mass spectrometry analysis, was formed by CYP2D4 and 2D6. The metabolism exhibited stereoselectivity. CYP2D1 and 2D4 selectively 8-hydroxylated the R(-)-enantiomer, and CYP2D6 predominately N-demethylated R(-)-enantiomer. N-Oxidation by CYP2D1 was specific to R(-)-enantiomer. In conclusion, CYP2D isoforms are involved in several metabolic pathways of mianserin acting in an isoform-specific manner. Stereoselectivity of the catalytic activities was clearly observed in the reactions of CYP2D1, 2D4, and 2D6.

Alcohol Oxidoreductases↗
PubMed1999

Developmental changes in the catalytic activity and expression of CYP2D isoforms in the rat liver.

Developmental changes in bufuralol 1'-hydroxylation activity, which is known as a typical activity of cytochrome P-450 (CYP)2D isoforms, in the liver of rats were investigated. The catalytic activities of hepatic microsomes increased with development especially from 3 to 7 weeks. Eadie-Hofstee plots of bufuralol 1'-hydroxylation were obtained for monophasic kinetics (Km: 0.037 microM) at 1 week and for biphasic kinetics (Km: 0.051 and 6.4 microM) at 7 weeks of age. Quinine completely inhibited bufuralol 1'-hydroxylation activity of hepatic microsomes of 1- and 7-week-old rats. These results indicated that at least two kinds of CYP2D isoforms, which differ markedly in their affinity for bufuralol, were present at 7 weeks of age and that the CYP2D isoform that had low affinity for bufuralol was expressed with development. To assess the affinity of CYP2D isoforms for bufuralol, the kinetic properties of CYP2D1, 2D2, 2D3, and 2D4 expressed in yeast cells were investigated. The Km value of CYP2D2, 0.044 microM, was extremely small compared with that of the other rat CYP2D isoforms. We further investigated developmental changes of CYP2D isoform mRNA by reverse transcription-polymerase chain reaction. CYP2D3 mRNA increased with development although CYP2D1 and 2D2 mRNA were not changed. The CYP2D4 mRNA was not detected. These findings indicated that CYP2D2, which had high affinity for bufuralol, was expressed in immature and mature rats, but CYP2D3, which had low affinity for bufuralol, was expressed only in mature rats.

Animals↗
PubMed1998

Deletion of bone marrow stromal cell antigen-1 (CD157) gene impaired systemic thymus independent-2 antigen-induced IgG3 and mucosal TD antigen-elicited IgA responses.

Bone marrow stromal cell Ag-1 (BST-1; CD157)-deficient mice were generated to examine the immunologic roles of the molecule in vivo. In BST-1(-/-) mice, the development of peritoneal B-1 cells was delayed, and CD38(low/-) B-lineage cells were increased in the bone marrow and spleen. Partial impairment of thymus-independent (TI-2) and thymus-dependent (TD) Ag-specific immune responses was noted in the systemic and mucosal compartments of BST-1(-/-) mice, respectively. Although serum Ig levels as well as TD and TI-1 Ag-specific systemic immune responses were normal, the TI-2 Ag-induced IgG3 response was selectively impaired. Oral immunization of BST-1(-/-) mice with cholera toxin, a potent TD Ag for the induction of IgA response, resulted in the poor production of Ag-specific Abs at the intestinal mucosa accompanied by the reduced number of Ag-specific IgA-producing cells in the lamina propria. These results indicate that BST-1 has roles in B cell development and Ab production in vivo.

ADP-ribosyl Cyclase↗
PubMed1998

Dopamine formation from tyramine by CYP2D6.

Dopamine is formed form L-tyrosine by tyrosine hydroxylase and aromatic L-amino acid decarboxylase. In addition to this pathway, however, the formation of catecholamines, including dopamine, from trace amines such as tyramine by hepatic microsomes has been demonstrated. In this study, we investigated the formation of dopamine from trace amines, using human hepatic microsomes and human cytochrome P450 (CYP) isoforms expressed in yeast. Among the 11 isoforms of human CYP expressed in yeast, CYP2D6 was the only isoform exhibiting strong ability to convert p-tyramine and m-tyramine to dopamine. In studies with human hepatic microsomes, the hydroxylation of tyramine to dopamine was inhibited by bufuralol, a typical substrate for CYP2D isoforms, and anti-CYP2D1 antiserum. This is the first report showing that CYP2D is capable of converting tyramine to dopamine. The Km values of CYP2D6, expressed in yeast, for p-tyramine and m-tyramine were 190.1 +/- 19.5 microM and 58.2 +/- 13.8 microM, respectively. Tyramine is an endogenous compound which exists in the brain as a trace amine but is also an exogenous compound which is found in foods such as cheese and wine. Our results suggest that dopamine is formed from endogenous and/or exogenous tyramine by this CYP2D isoform.

Animals↗
PubMed1998

Cloning and characterization of the CYP2D1-binding protein, retinol dehydrogenase.

A CYP2D1-binding protein, 29 k-protein (p29), has been isolated and its N-terminal amino acid sequence has been reported (Ohishi et al. (1993) Biochim. Biophys. Acta 1158, 227-236). In this study, p29 cDNA was isolated by PCR with oligonucleotide probes designed from the N-terminal amino acid sequence and p29 was found to be a microsomal retinol dehydrogenase, a member of the short-chain alcohol dehydrogenase family which metabolize hydroxysteroids and prostaglandins. CYP2D1 and p29 were expressed in Saccharomyces cerevisiae to characterize these proteins. CYP2D1 had an absorption maximum at 448 nm in a CO-reduced form. Expressed p29 in yeast cells was detected with anti-p29 antibody. Solubilized CYP2D1 and p29 from yeast microsomes were mixed and applied to an anti-CYP2D1 antibody-binding column. Both proteins were retained in the column and eluted with glycine buffer (pH 2.8). However, when applied alone, p29 was not retained in the column. The findings indicated that CYP2D1 bound tightly with p29. Catalytic activities of p29 expressed in yeast were investigated. p29 had retinal reductase activity in the presence of NADPH. Addition of CYP2D1 and NADPH-P450 reductase increased the retinal reductase activity of p29. These findings suggest that the complex of CYP2D1, p29, and NADPH-P450 reductase has an important role in the metabolism of retinoids.

Alcohol Oxidoreductases↗
PubMed1998

Tissue distributions of CYP2D1, 2D2, 2D3 and 2D4 mRNA in rats detected by RT-PCR.

The tissue distributions of four isoforms (CYP2D1/5, 2D2, 2D3 and 2D4/18) in rat CYP2D subfamily were investigated. Twelve kinds of tissue (liver, kidney, brain, lung, heart, spleen, adrenal gland, small intestine mucosa, bladder, testis, ovary and gonecystis) were removed from Sprague-Dawley male and female rats. The expression of CYP2D mRNA in these tissues was detected by RT-PCR. Specific primers were designed to recognize the four isoforms individually. In liver, kidney and small intestine mucosa, the mRNA expression of all four CYP2D isoforms was detected as high-intensity PCR products. mRNA of CYP2D1/5 was expressed in all tissues used in this study except the brain, although the intensity of PCR products varied among tissues. mRNAs of CYP2D2 and CYP2D3 were mainly expressed in liver, kidney and small intestine mucosa, which were exposed to xenobiotics such as drugs, food components and environmental contaminations. mRNA of CYP2D4/18 was expressed in liver, kidney, small intestine mucosa and brain. In brain, only mRNA of CYP2D4/18 was expressed. CYP2D4/18 mRNA was also expressed in ovary, testis and gonecystis. The tissue distributions help to clarify the differences in physiological and pharmacological functions between CYP2D isoforms.

Animals↗
PubMed1998

Nasal immune system: distinctive Th0 and Th1/Th2 type environments in murine nasal-associated lymphoid tissues and nasal passage, respectively.

The nasal mucosa, an important arm of the mucosal immune system, is the first site of contact with inhaled antigens to induce an IgA response. A major aim of this study was to characterize the Th1 and Th2 cytokine expression of mucosal T cells residing in nasal-associated lymphoid tissue (NALT) and nasal passages (NP) as IgA inductive and effector sites, respectively, at the transcription and cellular levels. An application of single-cell reverse transcription-PCR for analysis of Th1 (IFN-gamma) and Th2 (IL-4 and IL-6) cytokine-specific mRNA revealed the presence of CD4+ T cells with a Th0 profile in NALT, while high numbers of Th2 cytokine-specific mRNA expressed by CD4+ T cells were noted in NP followed by Th1-type cells. NALT CD3+ CD4+ T cells of Th0 type have the capacity to become Th1- and/or Th2-type cells since their activation via the TCR-CD3 complex resulted in the expression of an array of Th1 and Th2 cytokines. CD3+ CD4+ T cells from NP, but not NALT, provide a helper function for the induction of antibody-forming cells including IgA isotype in B cell cultures. These findings suggest that NALT is characterized by a Th0 environment which can gain a Th1 and/or Th2 phenotype. In contrast, NP is considered to be a Th2 dominant site with some Th1 cells that can support the induction of IgA-producing cells.

Animals↗
PubMed1998

Orally administered cholera toxin prevents murine intestinal T cells from staphylococcal enterotoxin B-induced anergy.

BACKGROUND & AIMS: Cholera toxin (CT) has been shown to be a strong mucosal adjuvant for the induction of antigen-specific secretory immunoglobulin A (IgA). The mechanism of adjuvant activity of CT is still unknown. The aim of this study was to examine the immunomodulatory function of CT on mucosal T cells using staphylococcal enterotoxin B (SEB) as coadministered oral antigen, because SEB has been shown to directly regulate alpha beta T-cell responses. METHODS: C3H/HeN mice were orally or systemically immunized with SEB and/or CT. The levels of SEB-specific antibodies and frequencies of CD4(+)Vbeta8(+) T cells were analyzed. SEB-specific T-cell proliferation and cytokine production were also determined. RESULTS: Neither SEB-specific IgA nor IgG antibodies were induced in feces when SEB was administered alone. This was a result of the clonal deletion and partial unresponsiveness of CD4(+)Vbeta8(+)T cells in Peyer's patches. On the other hand, SEB-specific antibodies were induced by oral immunization with SEB and CT. Although some degree of clonal deletion was induced by oral immunization with SEB and CT, coadministered CT prevented the induction of anergy for CD4(+)Vbeta8(+) T cells in Peyer's patches. CONCLUSIONS: CT is a powerful immunomodulatory molecule that prevents mucosal T cells from SEB-induced anergy.

Administration, Oral↗