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T Abo

Publications and source records attributed to T Abo.

At least 145 records · Page 8Linked to original sources
PubMed1995

Localization of porcine cardiac myosin epitopes that induce experimental autoimmune myocarditis.

Porcine cardiac myosin induced severe myocarditis in Lewis rats, similar to that seen after immunization with human or rat cardiac myosin. We investigated the localization of pathogenic epitopes by using porcine cardiac myosin. Subfragment-1 (S-1) and the rod were obtained by alpha-chymotryptic digestion. The rod was further fragmented by using cyanogen bromide cleavage. Three subfragments of S-1 were prepared by tryptic digestion. All Lewis rats immunized with the rod exhibited severe myocarditis, and the immunization of the cyanogen bromide-cleaved peptide equivalent to human beta-cardiac myosin heavy chain RDCB9 (residues 1070 to 1165) induced moderate myocarditis. Although none of the rats immunized with the whole S-1 exhibited any myocardial lesions, moderate inflammatory cardiac lesions were detectable in rats immunized with the tryptic digests of S-1. Our results indicate that the myocardiogenic epitopes in Lewis rats are located in the RDCB9 (residues 1070 to 1165) of the cardiac myosin rod and that a cryptic minor epitope may reside in S-1.

Amino Acid Sequence↗
PubMed1995

Characterization of intermediate T-cell receptor cells expanding in the liver, thymus and other organs in autoimmune lpr mice: parallel analysis with their normal counterparts.

Autoimmune MRL-lpr/lpr (lpr) mice were previously demonstrated to have an abnormal proliferation of intermediate T-cell receptor (TCR) cells of extrathymic origin in the liver. Despite this situation, thymectomy in lpr mice resulted in amelioration of autoimmune disease. To understand the underlying mechanism, we investigated associated T-cell differentiation in the thymus and other organs of these mice. When the disease was evoked, T cells with extrathymic properties, i.e. intermediate TCR-alpha beta cells expressing double-negative (DN) CD4-8- phenotype and interleukin-2 (IL-2) receptor beta-chain, became prominent not only in the liver, but also in the thymus. Such thymic T cells mainly resided in the medulla. A small-scale localization of such T cells was seen in the thymic medulla even in normal control mice. There was a heterogeneity among intermediate TCR cells in terms of the composition of DN cells and the expression of CD2 and B220 antigens, depending on the organs and the sites in the same organ. Intermediate TCR cells in the liver, thymus and autoimmune target organs (e.g. kidney) contained a high proportion of the active form (CD2+B220-), while intermediate TCR cells accumulating in peripheral organs, the spleen and lymph nodes, were mainly of the inactive form (CD2-B220+). The active form had an ability to proliferate in response to IL-2 and SEB, whereas the inactive form did not. The present results suggest that the proliferation of intermediate TCR cells occur at multiple sites; this may explain the effect of thymectomy, namely, the retarded onset of disease, in lpr mice.

Animals↗
PubMed1995

[The function and role of extrathymic T cells].

Murine liver contains alpha beta T cells with intermediate TCR (TCRint) as well as alpha beta T cells with bright TCR. Liver TCRint cells express NK1.1 Ag (NK1+ TCRint) and IL-2 receptor beta chain, both of which are NK cell markers and are not expressed on conventional T cells. Liver NK1+ TCRint cells consist of CD4-8- double negative T cells and CD4+ T cells and have V beta 8+ T cell preponderance. They are dependent on class Ib or CD1 molecules of APC for their development. They can also develop thymus independent manner, because athymic nude mice have this population. These NK1+ TCRint cells in the livers of both euthymic and athymic mice were found to be activated by systemic administration of IL-12 and increased NK1 expression (NK1high TCRint) and cytotoxicity against various NK-sensitive and resistant tumors. Cytotoxicity assays after treatment of IL-12 stimulated hepatic MNC with respective Abs and C revealed that CD4+ NK1high TCRint cells are responsible for IL-12 induced cytotoxicity. Although NK1+ TCRint cells were normally few in the lungs, a significant proportion of NK1high TCRint cells with strong cytotoxicity was also induced in the lung by IL-12. Interestingly, adoptive transfer of IL-12 stimulated hepatic MNC into other mice, which were pre-injected with tumors, inhibits hepatic metastases of EL4 cells and pulmonary metastases of 3LL cells as similarly as IL-12 administration. Transfer experiments after treatment of IL-12 stimulated hepatic MNC with respective Ab and C revealed that depletion of either NK1+ cells, CD3+ cells or CD4+ cells but not CD8+ cells greatly impaired antimetastatic effect in both organs. Thus, CD4+ NK1high TCRint cells are a major antimetastatic population, especially, against hematogenous metastases.

Animals↗
PubMed1995

Extrathymic T cells stand at an intermediate phylogenetic position between natural killer cells and thymus-derived T cells.

A series of recent studies have revealed that extrathymic pathways of T cell differentiation exist at multiple sites in mice and humans. In terms of their properties, extrathymic T cells may stand at an intermediate position between natural killer (NK) cells and thymus-derived T cells in phylogenetic development. It is speculated that primitive lymphocytes such as NK cells and extrathymic T cells develop from primordial macrophages in intraepithelial regions of e.g., the intestine, skin and liver. In this regard, the immune system of the bone marrow and thymus is relatively recent, developing after the emergence of living beings onto the land (i.e., amphibia). A complete elimination of self-reactive T cell clones occurs in mainstream intrathymic T cell differentiation and a consistent generation of such clones occurs through the extrathymic pathways. Therefore, thymus-derived T cells are efficient for processing foreign antigens, whereas extrathymic T cells recognize abnormal self-cells. Although thymus-derived T cells play the major role in youth, extrathymic T cells may play rather a pivotal role with aging and under conditions of malignancy, intracellular infections, pregnancy, and autoimmune diseases.

Animals↗
PubMed1994

Similarities and differences between extrathymic T cells residing in mouse liver and intestine.

Extrathymic T cells in the hepatic sinusoids and intraepithelial lymphocytes (IEL) in the intestine of mice have both similar and different properties. In this study, both types of extrathymic T cells in mice were further characterized. Lymphocytes obtained from systemic immune organs, including the lamina propria and Peyer's patches, were also compared. Extrathymic T cells in both the liver and the intestine contained a large proportion of gamma delta T cells and expressed the alpha alpha homodimer of CD8. They became more prominent in athymic nude mice and in normal mice with aging, while disappearing in scid mice. Extrathymic T cells in the liver, on the other hand, had TCR of intermediate intensity (i.e., intermediate TCR cells) and IL-2 receptor beta-chains (IL-2R beta) of high intensity, similar to NK cells, whereas IEL had TCR of bright intensity and consisted of cells with both low and high levels of IL-2R beta. Thymus-derived T cells did not express IL-2R beta at all, at least at their resting conditions. Intermediate TCR cells included double-negative CD4-8- cells as well as single-positive cells. In contrast, IEL contained both double-positive (DP) CD4+8+ cells and single-positive cells. More precisely, IEL gamma delta T cells were mainly IL-2R beta + and single-positive (mainly CD8+), while IEL alpha beta T cells were mainly IL-2R beta- and contained both DP CD4+8+ cells and single-positive cells. CD4+ cells were more predominant than CD8+ cells in the liver, while CD8+ cells were overwhelmingly predominant in the intestine. These results suggest that both intermediate TCR cells and IEL are generated as primitive T cells in phylogeny, but later develop along independent pathways at their respective sites.

Aging↗
PubMed1994

Glucocorticoid independence of acute thymic involution induced by lymphotoxin and estrogen.

Acute thymic involution is known to be induced under conditions of physical stress, bacterial infections, and malignancies. It is speculated that glucocorticoids, tumor necrosis factor (TNF), and other factors may act as mediators for the thymic involution under such conditions. It was herein investigated whether either lymphotoxin (TNF beta) or estrogen could induce thymic involution without the help of glucocorticoids. Interestingly, both lymphotoxin or estrogen alone induced profound thymic involution even in adrenalectomized mice. In contrast to glucocorticoids, which induce lymphocytopenia throughout the organs, lymphotoxin and estrogen did not induce lymphocytopenia in the peripheral organs. More importantly, lymphotoxin and estrogen rather stimulated extrathymic T cells in the liver and other organs. These results suggest that lymphotoxin and estrogen per se might be important regulators of immune systems.

Animals↗
PubMed1994

Predominant activation of extrathymic T cells during melanoma development of metallothionein/ret transgenic mice.

Transgenic mice that carried a metallothionein/ret fusion gene (Tg.MT/ret mice) exhibited severe pigmentation in their skin after birth and developed melanomas at adult ages. To learn how the immune system was modulated during melanoma development in these mice, lymphocytes in various organs were examined. An immunofluorescence cell analysis was focused on the simultaneous characterization of T cells of extrathymic and thymic origins and performed at three time points: 6 weeks of age (before melanoma development), 20 weeks (after melanoma development), and 30 weeks (end stage). The number and proportion of extrathymic T cells with TCR of intermediate intensity (i.e., intermediate TCR cells) were markedly increased in the liver over entire periods of life. These intermediate TCR cells constitutively expressed IL-2R beta, contained double-negative CD4-8- cells, and predominated V beta 8+ cells. Such intermediate TCR cells were also abundant among tumor infiltrating lymphocytes. In contrast, an increase in the number and proportion of regular T cells with TCR of bright intensity (i.e., bright TCR cells of thymic origin) was seen at only a limited period in various organs. Rather, at the late phase, thymic atrophy was induced and accompanied with the decrease in the proportion of bright TCR cells in the periphery. These results suggested that extrathymic T cells generated in the liver might play important roles in tumor immunity.

Animals↗
PubMed1994

T cell receptor peptide therapy for autoimmune encephalomyelitis: stronger immunization is necessary for effective vaccination.

Although T cell receptor (TCR) peptide therapy was initially reported to be a very effective method for prevention of the development of experimental autoimmune encephalomyelitis (EAE), it was recently demonstrated that the same peptide immunization led to enhanced and chronic EAE in some cases. In the present study, we examined the effect of the TCR peptide (V beta 8.2-39-59) vaccination on the development of EAE by employing several immunization protocols. We found that TCR peptide vaccination effectively prevented EAE development only when the peptide was injected with Mycobacterium tuberculosis-enriched CFA in the vicinity of the challenge site. Under such conditions, a sufficient number of peptide-reactive T cells were generated. Flow cytometry and immunohistochemical analyses using anti-peptide antibody and anti-V beta 8.2 mAb revealed that despite the presence of V beta 8.2+ cells, very few peptide-positive T cells appeared in the lymphoid organs throughout the course of EAE. These findings imply that antibodies that are generated after immunization with V beta 8P are hardly accessible to their specific epitopes in the native protein. Insufficient generation of both T cells and antibodies against V beta 8.2-positive T cells may be attributable to the outcome of the therapy. To establish effective TCR peptide immunotherapy, these disadvantages should be overcome by using other TCR sequences and/or by employing a more suitable adjuvant.

Adjuvants, Immunologic↗
PubMed1994

Lack of "determinant spread" to the minor encephalitogenic epitope in myelin basic protein-induced acute experimental autoimmune encephalomyelitis in the rat.

Acute and monophasic experimental autoimmune encephalomyelitis (EAE) was induced in rats by immunization with myelin basic protein (MBP). Proliferative responses of lymph node cells to major and minor encephalitogenic and nonencephalitogenic determinants of the MBP molecules were measured at various time intervals after the immunization. Results of these experiments revealed that additional responses to minor determinants which had been observed at the late stage of mouse EAE (Lehmann et al., Nature 356, 155, 1992) were very weak and short-lived in the rat. Furthermore, the response to the minor encephalitogenic determinant was not recognized throughout the course of EAE. Coimmunization with synthetic peptides, corresponding to the major and minor determinants, induced T-cell response only to the major determinant. These findings suggest that poor generation of T cells reactive with the minor encephalitogenic epitope is attributable to peptide competition between these two determinants. The present results, together with those reported in mice, strongly suggest that differences in the clinical course of EAE, i.e., acute monophasic or chronic relapsing, is closely related to the presence or absence of "determinant spread" to minor encephalitogenic epitope(s).

Acute Disease↗
PubMed1994

Female predominance of extrathymic T cells in mice: statistical analysis.

Female predominance of autoimmune diseases is widely known in humans and animals. To elucidate one of the underlying mechanisms, we examined whether sex differences exist at the level of extrathymic T cells in various organs of mice under physiological conditions. This attempt came from previous experimental results showing that estrogen administration to mice activates extrathymic T cells in the liver. Extrathymic T cells expressing TCR (and CD3) of intermediate intensity (i.e., intermediate TCR cells) and a high level of IL-2 receptor beta-chain (IL-2R beta), and thymus-derived T cells expressing TCR of bright intensity (i.e., bright TCR cells) and lacking IL-2R beta, were identified by immunofluorescent tests using mAbs. Three groups of different strains were examined. It was demonstrated that intermediate TCR cells were much more predominant in the liver and some other organs tested of female mice than of male mice, of each strain tested.

Animals↗
PubMed1994

Site- and strand-specific nicking at oriT of plasmid R100 in a purified system: enhancement of the nicking activity of TraI (helicase I) with TraY and IHF.

We developed a purified system for reproducing the nicking reaction at the site 59 base pairs upstream of the TraY protein binding site, sbyA, in the oriT region of plasmid R100. Nicking at oriT occurred efficiently in the presence of the plasmid-encoded proteins, TraI and TraY, integration host factor (IHF), and Mg2+, but inefficiently in the presence of the TraI protein and Mg2+. The products were complex DNA molecules with a protein covalently linked with the 5' end of the nick in the strand, which is supposed to be transferred during conjugation. The same complex DNA molecules were formed in the presence of the TraI protein alone, indicating that the protein attached at the 5' end of the nick is the TraI protein. Stimulation of the nicking reaction by the TraY protein and by IHF, whose binding site has been mapped between the nicking site and sbyA, indicates that DNA bending is important in the formation of the complex including the TraI and TraY proteins at oriT.

Bacterial Proteins↗
PubMed1994

Induction of specific unresponsiveness to cardiac allografts by short-term administration of anti-T cell receptor alpha beta antibody.

Organ graft rejection is a T cell-dependent process in which activation of alloreactive T cells via the T cell receptor/CD3 complex is a critical step. Although treatment with anti-CD3 has been shown to prevent and reverse allograft rejection, there is little information available regarding the effects of immunotherapy using anti-TCR alpha beta mAb for rejection. In the present study, short-term preoperative treatment of rats with a mAb against alpha beta TCR (R73) completely prevented the rejection of cardiac allografts. These rats accepted second cardiac allografts from the same donor strain, but not from a third-party strain, without additional treatment. In mixed lymphocyte cultures, T cells from rats that had received cardiac grafts did not respond to donor-strain heart cells, but did respond to donor-strain spleen cells and third-party heart cells. These findings suggest that specific unresponsiveness to cardiac tissue was induced in R73-treated rats. Such unresponsiveness was induced only when rats were pretreated with the mAb and subsequently received a transplant. It is likely that administration of a small dose of R73 induced transient immunomodulation of TCR molecules, resulting in unresponsiveness to a subsequent cardiac allograft. Immunotherapy with mAb against TCR alpha beta is very effective, without apparent side effects, and may provide a new method for preventing graft rejection.

Animals↗
PubMed1994

A similar expression pattern of adhesion molecules between intermediate TCR cells in the liver and intraepithelial lymphocytes in the intestine.

Two major populations of extrathymically differentiated T cells exist in the liver and intestine. Such T cells in the liver have TCR of intermediate intensity (i.e., intermediate TCR cells) and constitutively express IL-2 receptor beta-chain (IL-2R beta), whereas those in the intestine, especially intraepithelial lymphocytes, have TCR of bright intensity, consisting of a mixture of IL-2R beta+ and IL-2R beta-. All mature thymocytes and thymus-derived T cells seen in the peripheral immune organs are TCR-bright+ IL-2R beta- under resting conditions. When the expression pattern of adhesion molecules, including CD44, L-selectin, LFA-1 and ICAM-1, was compared among these T-cell populations, they displayed quite unique patterns of expression. All extrathymic T cells in the liver, intestine, and even other organs were CD44+ L-selectin-LFA-1++ICAM-1+, whereas thymocytes and thymus-derived T cells were CD44-L-selectin+LFA-1+ICAM-1-. This inverted expression of adhesion molecules between extrathymic T cells and thymus-derived T cells might be associated with their unique tissue-localization.

Animals↗
PubMed1994

Anti-alpha beta T cell receptor antibody prevents the progression of experimental autoimmune myocarditis.

We investigated the effects of anti-alpha beta T cell receptor antibody in rat experimental autoimmune myocarditis (EAM), using a new animal model of autoimmune myocarditis characterized by the appearance of multinucleated giant cells. EAM was induced by injecting Lewis rats subcutaneously in the footpads with 1.0 mg of human cardiac myosin in an equal volume of Freund's complete adjuvant (FCA) on days 0 and 7. In experiment 1, we evaluated the effect of long-term anti-alpha beta TCR antibody therapy on prevention of progression of EAM. Long-term administration of anti-alpha beta TCR antibody prevented progression of EAM in a dose-dependent manner. Flow cytometry performed at the time of sacrifice showed that the percentage of alpha beta T cells in lymph nodes and spleen was similar in the control group and the group in which almost no histologic evidence of myocarditis was found. In experiment 2, we examined the effects of short-term therapy. Rats were killed at different stages and pathologic specimens were examined. Short-term therapy delayed the onset of myocarditis. Results of flow cytometry suggested that impairment of antigen recognition or T cell function by occupancy of the TCR rather than depletion of TCR was the mechanism responsible for suppression of EAM.

Animals↗
PubMed1994

Increase in the proportion of granulated CD56+ T cells in patients with malignancy.

Evidence is presented for the existence of a unique T cell population which expressed one of the natural killer (NK) markers, CD56 antigen, in humans. Although such CD56+ T cells were a minor population in the peripheral blood (< 10%), they were abundant in the liver (up to 50%), which was recently demonstrated to be a major organ for extrathymic T cell differentiation in mice. As in the case of extrathymic T cells in mice, these CD56+ T cells in humans contained a higher proportion of gamma delta T cells than did CD56- T cells, contained double-negative CD4-8- cells, and had the morphology of large granular lymphocytes. This unique population of CD56+ T cells tended to be elevated in the blood and among tumour-infiltrating lymphocytes in patients with colorectal cancer, especially in advanced cases. These results raise the possibility that, as in mice, CD56+ T cells with extrathymic T cell properties may also be associated with tumour immunity in humans.

Adult↗
PubMed1994

Successful prevention and treatment of autoimmune encephalomyelitis by short-term administration of anti-T-cell receptor alpha beta antibody.

To identify an effective immunotherapy for T-cell-mediated autoimmune diseases, prevention and treatment of experimental autoimmune encephalomyelitis (EAE) induced in Lewis rats was attempted by administering a monoclonal antibody (mAb), R73, which is specific for rat T-cell receptor (TcR) alpha beta. Short-term administration of R73 at relatively low doses before immunization with encephalitogenic antigen, myelin basic protein (MBP), prevented the development of EAE. However, treatment with anti-CD4 and anti-Ia mAb in the same protocol was ineffective. Flow cytometric analysis demonstrated that short-term administration of R73 resulted in transient down-regulation of the TcR molecules, whereas the number of CD2-expressing T cells was well preserved. Furthermore, the response to MBP of T cells isolated from rats that were pretreated with R73 and then immunized with MBP was strongly suppressed. On the other hand, the T-cell response of R73-pretreated rats to a third-party antigen which was immunized at a later period was not inhibited. These findings suggest that in vivo administration of a low dose of R73 protects rats from EAE by inducing anergy of MBP-reactive encephalitogenic T cells. Furthermore, R73 treatment which started on day 10 of the immunization (shortly before the day of onset of clinical signs) completely suppressed the induction of EAE and that which started on day 11 (the day of onset) hastened recovery. Since the phenotypes of the TcR V beta chain of encephalitogenic T cells are not so limited as previously believed, immunotherapy with mAb against the TcR alpha beta framework may be one of the best methods for treatment of T-cell-mediated autoimmune diseases.

Amino Acid Sequence↗