Biomedical subjects

T Abo

Publications and source records attributed to T Abo.

At least 19 recordsLinked to original sources

PubMed1996

Extrathymic differentiation of resident T cells in the joints of mice with collagen-induced arthritis.

Murine collagen-induced arthritis (CIA) is known as a T cell-mediated autoimmune disease, although autoantibodies are also suspected to be associated with the onset of the disease. To determine the origin of such T cells in the joints of mice with CIA, their phenotypic properties as well as those of T cells in other immune organs were examined in DBA/1 mice. Since a significant number of mononuclear cells (MNC) was also yielded by the joints of normal DBA/1 mice, the properties of these T cells were examined in parallel. When CIA was induced by an intradermal injection of type II collagen at the base of the tail, the numbers of MNC yielded by the regional lymph nodes and the foot joints were doubled. Interestingly, regardless of the onset of CIA, the joints were always comprised of unique T cell populations, including IL-2(R)alpha- beta+ T cells, gammadelta T cells, CD8alpha+ beta- cells, and CD44+ L-selectin- cells. All these properties coincide with those of extrathymic T cells in liver and intestine. In the case of gammadelta T cells in joints, Vgamma and Vdelta usages were unique and different from those in the other organs. More importantly, Vgamma and Vdelta usages in gammadelta T cells in the joints of normal mice and in those of mice with CIA were essentially the same. Taken together with the expression of recombination-activating gene-1 and -2 mRNAs by MNC in mice with CIA, these findings raise the possibility that the joints have their own resident T cells that are extrathymically generated in situ.

Animals↗

PubMed1996

Simultaneous activation of granulocytes and extrathymic T cells in number and function by excessive administration of nonsteroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) sometimes show serious side effects such as damage to the gastroduodenal mucosa and dysfunction of the liver. Although many investigators have focused on some types of leukocytes, a comprehensive study concerning all types of leukocytes, especially recently identified extrathymic T cells, remains to be done. When mice were treated with an intraperitoneal injection of indomethacin (50 or 300 microg/mouse), the number of thymocytes decreased while the number of MNC in various peripheral organs increased. This increase in MNC was due mainly to the increase in the numbers of granulocytes and extrathymic T cells. Reflecting thymic atrophy, the proportion of thymus-derived T cells distributed in the periphery decreased. The use of other NSAIDs revealed that granulocytosis seen in the periphery arose from a selective activation of myelomonocytic cells in the bone marrow. Some functional experiments using the Ca2+ influx, iNOS mRNA expression, and autoreactive cytotoxicity as indicators suggested that granulocytes and extrathymic T cells were in activated states not only in number but also in function. Since both granulocytes and extrathymic T cells become cytotoxic effectors against self-tissues or self-cells when overactivated, these activated leukocytes may be intimately related to the etiology of the tissue damage inducible by NSAIDs (i.e., adverse drug reaction).

Animals↗

PubMed1996

Level of myelopoiesis in the bone marrow is influenced by intestinal flora.

Mice were orally given kanamycin (50 mg/day/ mouse) for 1 or 2 weeks. Almost all bacteria in the intestine were eliminated within a week. In parallel with this elimination, the level of granulocytes in the bone marrow decreased from 41 to 31%. Since the total number of bone marrow cells decreased as well (up to one-third), the decrease in the level of granulocyte generation in the bone marrow was substantial. Kanamycin is not absorbed from the intestine into the body; namely, it does not have a direct effect on the bone marrow. It is speculated that the interaction of granulocytes or epithelial cells with intestinal bacteria accelerates the production of free radicals and superoxids, some cytokines, or unknown factors and that such substances then stimulate the generation of granulocytes in the bone marrow. The present results suggest that intestinal flora and other resident bacteria are important for maintaining the level of myelopoiesis in the bone marrow.

Animals↗

PubMed1996

Physiological dose of estrogen regulates extrathymic T cells in female mice.

Bilateral ovariectomy was performed in female C57BL/6 mice to investigate whether extrathymic T cells in the liver are regulated by physiological doses of estrogen or progesterone. Extrathymic T cells were identified using a two-color immunofluorescence test for CD3 and interleukin-2 receptor beta-chain (IL-2R beta) antigens. The T cells were identified as intermediate CD3+ cells with a high expression of IL-2R beta. It was further demonstrated that the proportion and number of intermediate CD3+ cells decreased in response to ovariectomy, an effect that was countered by estrogen administration. These results suggest that the activation of extrathymic T cells may be regulated by physiological levels of estrogen.

Animals↗

PubMed1996

c-kit+ stem cells and thymocyte precursors in the livers of adult mice.

Livers of the adult mice contain c-kit+ stem cells that can reconstitute thymocytes, multiple lineage cells, and bone marrow (BM) stem cells. Transfer of 1 x 10(7) hepatic mononuclear cells (MNC) and 5 x 10(4) hepatic c-kit+ cells of BALB/c mice induced DP thymocytes within a week in four Gy-irradiated CB17/-SCID mice, but 2 wk were required for BM cells or BM c-kit+ cells to produce DP thymocytes. Moreover, B cell-depleted BM cells or liver MNC of SCID mice that had been rescued by hepatic MNC of BALB/c mice again reconstituted thymus and B cells of other irradiated SCID mice. CD3- IL-2R beta- populations of both BM cells and hepatic MNC of C57BL/6 (B6) mice could generate T cells with intermediate TCR (mostly NK1.1-) in the liver of irradiated B6 SCID mice before thymic reconstitution (extrathymic T cells). Furthermore, transfer of liver c-kit+ cells of B6-Ly 5.1 mice into irradiated B6 SCID (Ly5.2) mice revealed that liver c-kit+ cells can reconstitute myeloid and erythroid lineage cells. These results strongly suggest that the liver contains pluripotent stem cells and serves an important hematopoietic organ even into adulthood.

Animals↗

PubMed1996

A comparison of proliferative response to IL-7 and expression of IL-7 receptors in intermediate TCR cells of the liver, spleen, and thymus.

It is well established that IL-7 supports the earliest differentiation of both T and B cells in fetal and adult life. On the other hand, mature lymphocyte subsets tend to decrease the response to IL-7 in case of T and B cells. In a recent study, NK1.1+ T cells in the thymus are also found to efficiently respond to IL-7 and express IL-7 receptors (IL-7R). This population is generated through an alternative intrathymic pathway. A similar population, namely, T cells with intermediate levels of TCR (i.e., int TCR cells) are known to be generated through extrathymic pathways. In this respect, the proliferative response to IL-7 and the expression of IL-7R in int TCR cells of various organs were compared. Whole liver MNC and isolated int TCR cells from the liver were found to proliferate in response to IL-7. Moreover, a considerable population of int TCR cells in both the liver and thymus were found to carry a higher density of IL-7R on the surfaces than high TCR cells. More precisely, the intensity of IL-7R on int TCR cells in the thymus was the highest but those on int TCR cells in other organs were slightly lower (i.e., int TCR cells in the thymus greater than int TCR cells in the liver greater than high TCR cells). Taken together with the result of expression of IL-7 mRNA by hepatocytes and thymic tissues, it is concluded that IL-7 is one of the most important growth factors for int TCR cells both in the liver and thymus.

Animals↗

PubMed1996

Characterization of CD4-CD8- T cell receptor alpha beta + T cells appearing in the subarachnoid space of rats with autoimmune encephalomyelitis.

Inflammation of the central nervous system (CNS) in experimental autoimmune encephalomyelitis (EAE) starts in the subarachnoid space (SAS) and spreads later to the adjacent CNS parenchyma. To characterize the nature of lesion-forming T cells in situ in more detail, T cells were isolated from the SAS and their surface phenotype and the nucleotide sequence of the junctional region of the T cell receptor (TCR) was determined and compared with those of the lymph node (LN) and spinal cord (SC) T cells. Characteristically, more than 70% of SAS TCR alpha beta + T cells isolated at the early stage of EAE lacked both CD4 and CD8 molecules, whereas those from LN and SC were either CD4+ or CD8+. Analysis of nucleotide sequences of the junctional region of TCR revealed that T cells bearing a sequence identical to that for encephalitogenic T cell clones were found in both SAS and SC. Furthermore, purified CD4-CD8- T cells expressed CD4 molecules after culture. At the same time, these T cells acquired reactivity to myelin basic protein and induced passive EAE in naive animals after adoptive transfer. Our results suggest that CD4-CD8- T cells in the SAS are precursors of lesion-forming T cells in the SC and that phenotype switching takes place during the process of T cell infiltration into the CNS parenchyma. The double-negative nature of these T cells may explain an escape of encephalitogenic T cells from negative selection in T cell differentiation.

Amino Acid Sequence↗

PubMed1996

Existence of a small population of IL-2R beta hi TCRint cells in SCG and MRL-lpr/lpr mice which produce normal Fas mRNA and Fas molecules from the lpr gene.

Mice carrying the lpr gene, SCG and MRL-lpr/lpr mice, were used to characterize the phenotype and lpr gene of abnormally proliferating T cells in these mice. A major population which expanded in these mice were T cells expressing intermediate (int) levels of T cell receptor (TCR) (and CD3) and the phenotype of interleukin-2 receptor (IL-2R) beta lo alpha- (possibly abnormal TCRint cells). The levels of TCRhi cells of thymic origin (generated through the mainstream of T cell differentiation in the thymus) profoundly decreased after the onset of disease. However, a small population of normal TCRint cells (i.e. IL-2R beta hi alpha-) were also found to exist in all tested organs. For example, the majority of abnormal IL-2R beta lo TCRint cells were CD4-8- CD2-, while normal IL-2R beta hi TCRint cells were a mixture of single-positive cells (mainly CD8+), CD4-8- cells and CD2+ cells. Moreover, normal TCRint cells preferentially produced normal Fas mRNA and Fas molecules from the lpr gene. This phenomenon explains the leaky appearance of normal Fas mRNA and Fas molecules in mice carrying the lpr gene. It is suggested that a small population of IL-2R beta hi TCRint cells are resistant to the lpr genetic abnormality.

Animals↗

PubMed1996

Intraepithelial lymphocytes in colon have similar properties to intraepithelial lymphocytes in small intestine and hepatic intermediate TCR cells.

Recently, properties of intraepithelial lymphocytes (IEL) in the colon (C-IEL) have been analyzed in comparison with those of IEL in the small intestine (SI-IEL). We compared the properties of C-IEL with those of SI-IEL and hepatic intermediate TCR cells, two other types of extrathymic T cells. C-IEL and intermediate TCR cells contain many NK1+T cells, although SI-IEL contain few. V gamma and V delta usage of C-IEL was the same as that SI-IEL, and that of intermediate TCR cells was different. C-IEL responded to Con A while SI-IEL did not. As to adhesion molecules, C-IEL include both extrathymic and thymus-originated type T cells. With age, TCR- alpha beta(+) CD4+ CD8+ cells do not increase among C-IEL but do increase among SI-IEL. IL-2R beta(+) or CD4- CD8- C-IEL increase as observed in the liver. These results indicate that these organ-specific T cells have different roles at their respective sites and that they may be of different lineages.

Animals↗

PubMed1996

Cytotoxic activity against tumour cells mediated by intermediate TCR cells in the liver and spleen.

Morphological and phenotypic characterization in previous studies has indicated that intermediate (int) T-cell receptor (TCR) cells or T natural killer (TNK) cells may stand at an intermediate position between NK cells and high TCR cells of thymic origin in phylogenetic development. In this study, a functional study on cytotoxic activity against various tumour targets was performed in each purified subset. When a negative selection method entailing in vivo injection of anti-asialo GM, antibody or anti-interleukin (IL)-2R beta monoclonal antibody (mAb) was applied, IL-2R beta 1 CD3 NK cells were found to have the highest NK activity while IL-2R beta 1 int CD3 (or TCR) cells had a lower level of the NK activity. High CD3 cells (freshly isolated) did not have any such activity. Sorting experiments further revealed that the NK function mediated by int CD3 cells was augmented when they were exposed to anti-CD3 mAb. anti-TCR alpha beta, or anti-TCR-delta mAb. This phenomenon was not observed in NK cells and high CD3 cells. More importantly, when anti-CD3 mAb (or anti-TCR mAb) was added to the assay culture, int CD3 cells became cytotoxic against even NK-resistant tumour (Fc gamma R-. Fas+) targets. Liver mononuclear cells or int CD3 cells exposed to anti-CD3 mAb for 6 hr showed an elevated level of perforin in their cytoplasms. The present results suggest that int CD3 cells are usually non-cytotoxic against various tumours but become functional after being stimulated via the TCR CD3 complex.

Animals↗

PubMed1996

Kinetics of organ-associated natural killer cells and intermediate CD3 cells during pulmonary and hepatic granulomatous inflammation induced by mycobacterial cord factor.

We investigated here the kinetics of natural killer (NK) cells and extrathymic T cells, which include intermediate CD3 cells and gamma delta T cells, in the cord factor-induced granulomatous inflammation of the lungs and liver. In Balb/c mice, pulmonary inflammation elevated the proportion of NK cells and that of extrathymic T cells to mononuclear cells in the lungs. C3H/He mice exhibited shorter-term inflammation of the lungs than Balb/c mice and accordingly showed a smaller increase in the proportions of pulmonary NK cells and intermediate CD3 cells. In the liver of Balb/c mice, hepatic NK cells increased as well with the granulomatous changes, while intermediate CD3 cells exhibited a transient decrease before they increased. The present study has demonstrated that granulomatous inflammation is accompanied by the increase of lung-associated NK cells and extrathymic T cells and that there exists a difference between these two mouse strains in the induction of these lymphocyte subsets by cord factor.

Animals↗

PubMed1996

Analysis of heart-infiltrating T-cell clonotypes in experimental autoimmune myocarditis in rats.

Experimental autoimmune myocarditis (EAM) resembles the lethal giant cell myocarditis seen in humans, and the recurrent forms lead to dilated cardiomyopathy (DCM). EAM in rats induced by a subcutaneous injection of cardiac myosin has been shown to be a T cell-mediated autoimmune disease. Alpha beta T cells have proved to be important by the observation that antibodies to alpha beta T-cell receptor (TCR) prevent disease progression. Alpha beta cells recognize antigenic peptides bound to major histocompatibility (MHC) molecules by alpha beta TCR, and complementarity determining region 3 (CDR3) is considered the most important region for antigen recognition. To elucidate the nature of this T cell-mediated myocarditis, we analyzed TCR V beta chains of heart-infiltrating T cells. In the early state of EAM, none of 22 TCR V beta chain transcripts seemed to be dominant by reverse transcription-polymerase chain reaction analysis of total RNA and flow cytometric analysis. On the other hand, single-strand conformation polymorphism analysis of TCR V beta 8.2, V beta 8.5, V beta 10, and V beta 16 cDNA amplified by polymerase chain reaction encompassing the CDR3 revealed oligoclonal expansion in heart-infiltrating T cells isolated from animals at various disease stages. cDNA encoding V beta CDR3 from heart-infiltrating and pericardial effusion T cells in rats with EAM revealed more restricted sequences than did cells from rats with normal spleens. Clones from distinct lesions of the same animal were identical, and clones from heart-infiltrating and pericardial effusion T cells from the same animal showed overlap. Thus, CDR3 of the TCR beta chain may be important in rat EAM, and heart infiltrating T cells are considered to recognize the specific antigen.

Amino Acid Sequence↗

PubMed1995

Relationships between intermediate TCR cells and NK1.1+ T cells in various immune organs. NK1.1+ T cells are present within a population of intermediate TCR cells.

Experiments to date have revealed a population of T cells that carry intermediate (int) levels of TCR (or CD3) and express IL-2R beta-chain (IL-2R beta) in mouse liver. Such int TCR cells also reside in other immune organs, although in low numbers. On the other hand, NK1.1+ T cells with int TCR do reside in the thymus and other peripheral organs. To determine the relationship of two types of cells, we characterized int CD3 cells and NK1.1+ T cells throughout the organs in terms of the phenotype, V beta repertoire, and morphology. Although both IL-2R beta+ T cells and NK1.1+ T cells are classified as int CD3 cells, NK1.1+ T cells are present within int CD3 cells. The majority of int CD3 cells in the liver and thymus were NK1.1+, whereas the minority of such cells in the spleen, lymph nodes, and bone marrow were NK1.1+. Among int CD3 cells, double-negative (DN) CD4-8- cells and/or CD4+ were abundant in NK1.1+ subset, whereas CD8+ cells were generally abundant in NK1.1- subset. Self-reactive V beta+ clones estimated by the M1s system were distributed to both NK1.1+ and NK1.1- subsets. High CD3 cells in the thymus and other organs contained neither DN cells nor forbidden clones. Int CD3 cells had the morphology of granular or agranular lymphocytes carrying perforin. Among int CD3 cells, NK1.1+ subset had a higher level of perforin-positive cells than NK1.1- subset. These results clearly demonstrate the relationship between int TCR cells and NK1.1+ T cells in various organs.

Animals↗

PubMed1995

Evidence for extrathymic generation of intermediate T cell receptor cells in the liver revealed in thymectomized, irradiated mice subjected to bone marrow transplantation.

In addition to the major intrathymic pathway of T cell differentiation, extrathymic pathways of such differentiation have been shown to exist in the liver and intestine. In particular, hepatic T cells of T cell receptors or CD3 of intermediate levels (i.e., intermediate T cell receptor cells) always contain self-reactive clones and sometimes appear at other sites, including the target tissues in autoimmune diseases and the tumor sites in malignancies. To prove their extrathymic origin and self reactivity, in this study we used thymectomized, irradiated (B6 x C3H/He) F1 mice subjected to transplantation of bone marrow cells of B6 mice. It was clearly demonstrated that all T cells generated under athymic conditions in the peripheral immune organs are intermediate CD3 cells. In the case of nonthymectomized irradiated mice, not only intermediate CD3 cells but also high CD3 cells were generated. Phenotypic characterization showed that newly generated intermediate CD3 cells were unique (e.g., interleukin 2 receptor alpha-/beta+ and CD44+ L-selectin-) and were, therefore, distinguishable from thymus-derived T cells. The precursor cells of intermediate CD3 cells in the bone marrow were Thy-1+ CD3-. The extrathymic generation of intermediate CD3 cells was confirmed in other combinations of bone marrow transplantation, C3H --> C3H and B10.Thy1.1 --> B6.Thy1.2. The generated intermediate CD3 cells in the liver contained high levels of self-reactive clones estimated by anti-V beta monoclonal antibodies in conjunction with the endogenous superantigen minor lymphocyte-stimulating system, especially the combination of B6 --> (B6 x C3H/He) (graft-versus-host-situation).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Synchronous expansion of intermediate TCR cells in the liver and uterus during pregnancy.

The immunophysiology of pregnancy was investigated in relation to how extra- and intrathymic pathways of T cell differentiation are modulated during pregnancy. Pregnancy was produced in syngeneic and allogeneic combinations in mice. In both cases, a prominent decrease in the number of thymocytes and a mild increase in the number of hepatic mononuclear cells (MNC) were induced during the periparturient period. The most striking change was the increase in the number of intermediate TCR cells with extrathymic T cell properties in the liver. When MNC yielded by the uterus were examined, an expansion of intermediate TCR cells was also observed in this organ during pregnancy. The major populations in the pregnant uterus were NK cells and intermediate TCR cells, the latter of which contained double-negative CD4-8- cells and consisted of both alpha beta and gamma delta T cells. All of these properties coincided with those of extrathymic T cells in the liver. Reflecting extrathymic T cell differentiation, MNC in the liver and pregnant uterus expressed mRNA of RAG-1 and RAG-2. To determine the role of hormonal regulation in this phenomenon, the effects of various pregnancy-associated hormones on thymocytes and hepatic MNC were examined in nonpregnant mice. Of the hormones tested, estrogen was found to induce a response similar to that seen in pregnant mice. These results suggest that a local immune response in the uterus during pregnancy is a phenomenon occurring synchronously with systemic immune systems.

Animals↗

PubMed1995

Long-term survival of cardiac allografts in rats treated before and after surgery with monoclonal antibody to CD2.

The rejection of a transplanted allograft is dependent on T cell activation, which requires T cell receptor engagement by antigen and costimulatory signals delivered by T cell surface molecules such as CD2. Anti-CD2 mAbs have been shown to suppress cell-mediated immunity. The effects of anti-CD2 mAbs OX34 and OX54 on rejection of BN (RT1n) rat hearts transplanted heterotopically to LEW (RT1l) rats were investigated. Administration of OX34 (7 mg/kg/day i.p.), either for 3 consecutive days immediately before or 8 consecutive days immediately after transplantation induced indefinite allograft survival (median survival time: 7, > 150, and > 150 days for control, preoperative treatment, and postoperative treatment, respectively). In contrast, pre- or postoperative treatment with OX54 (40 mg/kg/day) prolonged median survival time to only 28 and 11 days, respectively. Administration of OX34 or OX54 to naive rats induced a transient depletion of T cells in the peripheral immune organs. In vitro studies revealed that whereas OX54 had no effect on the allogeneic mixed lymphocyte reaction, OX34 partially inhibited both the allogeneic mixed lymphocyte reaction, in an IL-2-reversible manner, and T cell proliferation in response to immobilized mAb to either the T cell receptor or CD3. OX34-treated rats in which the cardiac allograft had survived > 100 days accepted a second heart from the donor strain. Treatment with OX34 induced an alloantigen-unresponsive state in T cells. These results suggest that treatment with an appropriate anti-CD2 mAb, especially postoperatively, may prove an effective approach for preventing cardiac allograft rejection.

Animals↗

PubMed1995

Self-reactive T cell clones in a restricted population of interleukin-2 receptor beta+ cells expressing intermediate levels of the T cell receptor in the liver and other immune organs.

T cells expressing high levels of the T cell receptor (TCRhigh) differentiate in the major intrathymic pathway and then distribute to the peripheral immune organs, whereas T cells expressing intermediate levels of the TCR (TCRint) differentiate in both extrathymic pathways and an alternative intrathymic pathway and localize in unique sites, including the liver and thymic medulla. Since TCRint cells constitutively express interleukin-2 receptor beta-chain (IL-2R beta), two-color staining for CD3 (or TCR) and IL-2R beta clearly distinguished IL-2R beta+ CD3int (or TCRint) cells from IL-2R beta-, CD3high cells. CD3int cells may be considered to be primordial T cells based on their phenotype, morphology and other functional properties. In this study, using anti-V beta mAb in conjunction with the endogenous superantigen Mls, the distribution of self-reactive clones among T cells generated in all of the above pathways was investigated in mice. Self-reactive T cell clones were confined to IL-2R beta+, CD3int cells, in all of the organs tested. A significant proportion of self-reactive clones was never identified among CD3high cells in the thymus and peripheral immune organs in either young (8 week old) or old (50 week old) mice. Possibly reflecting their self-reactivity, CD3int cells, but neither NK cells nor CD3high cells had a potent cytotoxic effect against a syngeneic hepatoma in the presence of anti-CD3 mAb. These results raise the possibility that CD3int cells seen in the liver and thymus might belong to a similar primordial lineage of T cells, and that self-reactive clones are not generated through the major intrathymic pathway, but only through extrathymic pathways and an alternative intrathymic pathway.

Age Factors↗

PubMed1995

Unique order of the lymphocyte subset induction in the liver and intestine of mice during Listeria monocytogenes infection.

We investigated how NK cells, extrathymic T cells, and thymus-derived T cells are activated in mice during infection with an intracellular pathogen, Listeria (L.) monocytogenes. Although macrophages and granulocytes are known to be involved in the elimination of this pathogen in an early phase of infection, it was still controversial what type of lymphocytes are induced as effectors in subsequent phases. When mice were ip injected with 1 x 10(3) L. monocytogenes (a sublethal dose), a prominent increase in the number of mononuclear cells in the liver and spleen was induced. Phenotypic analysis revealed that serial induction of lymphocyte subsets, NK cells-->extrathymic T cells-->thymus-derived T cells, occurred in these organs. Extrathymic T cells were estimated to have intermediate CD3 and a high level of IL-2 receptor beta-chain on the surface (i.e., intermediate CD3 cells). These mice became free from infection after 2 weeks. In the case of oral administration, 1 x 10(3) L. monocytogenes increased the number of cells in the liver and the number of intraepithelial and lamina propria lymphocytes in the intestine. Phenotypic analysis also showed a sequential induction of lymphocyte subsets in the liver and the induction of extrathymic T cells in the intestine. Preelimination of intermediate TCR cells and NK cells by in vivo treatment with anti-LFA-1 mAb made mice susceptible to an ip injected sublethal dose of L. monocytogenes. These results reveal a unique order of lymphocyte induction during listerial infection and indicate that extrathymic T cells might be one of the important cells in achieving resistance against L. monocytogenes.

Animals↗