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T Abo

Publications and source records attributed to T Abo.

At least 181 records · Page 10Linked to original sources
PubMed1992

Age-dependent increase of extrathymic T cells in the liver and their appearance in the periphery of older mice.

The liver is a major site of generation of extrathymic T cells with unique properties (e.g., expressing intermediate TCR and containing self-reactive clones). We investigated herein whether the levels of extrathymic alpha beta T cells varied in various organs as a function of age. A systematic examination of the number of mononuclear cells in various organs of BALB/c mice revealed that the number of hepatic MNC increased with age whereas the number of thymocytes decreased. These changes were more striking in mice fed under conventional conditions than under specific pathogen-free condition. The age-dependent changes in the number of mononuclear cells in the spleen and lymph nodes were minimal. Although the total proportion of alpha beta T cells in each organ remained constant, the staining patterns of TCR-alpha beta as shown by immunofluorescence profiles varied. The most prominent change was that intermediate TCR-alpha beta cells, which constituted a small population in the liver of young mice, expanded in the liver of older mice. Intermediate TCR cells appeared even in the periphery of older mice. These findings were confirmed by the appearance of extrathymic T cells with other unique properties, e.g., double-negative CD4-8- phenotype and CD44 expression. In athymic nude mice, only intermediate TCR cells were present in the liver and periphery. An age-dependent increase of intermediate TCR cells was also seen in these mice. Taken together with the result of bromodeoxyuridine-injection experiment, which showed an intensive in vivo proliferation of cells in the hepatic sinusoids, extrathymic T cells may differentiate predominantly in the liver and appeared even to the periphery in older mice.

Age Factors↗
PubMed1992

Estrogen administration activates extrathymic T cell differentiation in the liver.

In addition to T cell differentiation in the thymus, we have recently reported that extrathymic T cell differentiation occurs preferentially in the sinusoids of the liver. Although this extrathymic pathway is relatively minor in normal mice, it becomes predominant in mice with autoimmune diseases, athymic mice, and aged mice. In the present study, injection of normal male C3H/He mice, 6-8 wk of age, with 1 mg of estrogen resulted in an increase in mononuclear cells (MNC) yielded from the liver and a drastic decrease in thymocytes approximately 10 d after such injection. This unique modulation was not observed with hydrocortisone injection (5 mg/mouse, i.p.) nor with irradiation (5 Gy/mouse). Rather, these immunosuppressive treatments induced a simultaneous decrease in cell number in both the liver and thymus. A time-kinetics study on the cell number and spontaneous cell proliferation revealed that an increase in spontaneous cell proliferation in the liver preceded the increase in the number of liver MNC, and a decrease in spontaneous cell proliferation in the thymus preceded the decrease in the number of thymocytes. At this time, an enrichment of alpha/beta T cells with intermediate T cell receptors (TCRs), including forbidden T cell oligoclones and V beta 8+ cells, which are characterized as extrathymic alpha/beta T cells with unique properties, took place in the liver. On the other hand, the thymic atrophy induced by estrogen resulted in a prominent decrease in immature double-positive (CD(4+)8+) alpha/beta T cells with dull TCRs. These results indicate that estrogen administration activates an extrathymic pathway of T cell differentiation in the liver and reciprocally inactivates the intrathymic pathway. As extrathymic T cells have unique characteristics such as autoreactivity, the present findings might be intimately related to a female predominance of autoimmune diseases and suggest a possible role of estrogen in this phenomenon.

Animals↗
PubMed1992

Details of an isolation method for hepatic lymphocytes in mice.

The liver comprises a unique lymphocyte population, i.e., extrathymic alpha beta T cells with TcR of intermediate intensity. In the present study, we attempted to determine what pretreatments were appropriate to isolate hepatic mononuclear cells (MNC) containing such intermediate alpha beta TcR cells in mice. Hepatic MNC were isolated from untreated mice and mice subjected to either bleeding or liver perfusion, and the intermediate alpha beta TcR cells in each preparation were identified. For reasons of simplicity, cell purity and cell yields, hepatic lymphocytes should be obtained from mice subjected to total bleeding. Additional information on extrathymic alpha beta T cells obtained by using the recommended method is also presented.

Animals↗
PubMed1992

Selective activation of extrathymic T cells in the liver by glycyrrhizin.

Extrathymic pathways for T cell differentiation were recently demonstrated in the liver, intestine and omentum. In this study, glycyrrhizin (GL), a plant extract was investigated as to its effect on extrathymic T cells in the liver of mice. A new method using anti-LFA-1 mAb in conjunction with anti-TCR or -CD3 mAbs to sensitively identify such extrathymic T cells is included. Single injection and repeated injections of GL increased not only the number of total hepatic MNC but also the proportion of intermediate TCR cells, which are extrathymic T cells uniquely seen in the liver. In contrast to other tested reagents (e.g., lymphotoxin and estrogen) that activated the extrathymic T cells and simultaneously induced profound thymic atrophy, GL did not affect regular T cells in the thymus. The present results suggest that the selective activation of extrathymic T cells in the liver might be intimately related to the clinical effects of GL.

Animals↗
PubMed1992

Activation of extrathymic T cells in the liver and reciprocal inactivation of intrathymic T cells by bacterial stimulation.

We recently demonstrated that the liver might be a major site of extrathymic T cell differentiation, including both alpha beta and gamma delta T cells. This extrathymic pathway in the liver, which has a relatively minor role in normal young mice, is activated in mice under bacterial stimulation. In the present study, we investigated how the extrathymic and intrathymic T cell differentiations were mutually related in mice injected intravenously with 10(8) heat-killed Escherichia coli. Three days after stimulation, extrathymic T cells in the liver were observed to be prominently activated in terms of increases in the total number of cells yielded, spontaneous cell proliferation in in vitro culture, and intermediate alpha beta TCR cells. Intermediate alpha beta TCR cells were extrathymic T cells uniquely seen in the liver. However, at the same time intrathymic T cells were profoundly inactivated, showing decreases in the number of thymocytes (more than 90% atrophy), spontaneous cell proliferation, and dull TCR cells with double positive CD4+8+ phenotype. With time, these responses were reversed and normal states were regained. These results suggested that extrathymic and intrathymic T cells are always activated or inactivated in the opposite direction, and that the liver and the thymus are dynamic immune organs. It raises the possibility that the extrathymic T cell differentiation in the liver and the intrathymic T cell differentiation may be reciprocally regulated by certain factors.

Animals↗
PubMed1992

Relative resistance of intermediate TCR cells to anti-CD3 mAb in mice in vivo and their partial functional characterization.

In addition to T cells differentiated in the thymus, T cells, possibly of extrathymic origin, were recently demonstrated in the liver of mice. These T cells are characterized by the expression of intermediate TCR and contain double-negative CD4-8- cells. A further characterization of intermediate TCR cells was carried out. When mice were injected ip with anti-CD3 mAb, bright TCR cells (i.e., regular T cells) and intermediate TCR cells were reduced on Day 3, depending on the amount of mAb. Because of the resistance of intermediate TCR cells to treatment, injection of an appropriate dose of antibody (i.e., 100 micrograms/mouse) eliminated most bright TCR cells, but not intermediate TCR cells. This dose revealed that a significant proportion of intermediate TCR cells also reside in the periphery. Hepatic and splenic mononuclear cells (MNC), in which intermediate TCR cells became abundant after treatment, showed a unique response to T cell mitogens and IL-2. Thus, the intermediate TCR cell-enriched population could not respond to a T cell mitogen, Con A, but responded well to a super antigen, staphylococcal enterotoxin B, and IL-2. MNC obtained from athymic nude mice, which comprise only intermediate TCR cells, responded in the same manner. These findings revealed that intermediate TCR cells are present not only in the liver but also in the periphery, and that they have a unique function distinct from regular T cells.

Animals↗
PubMed1992

Lymphotoxin activates hepatic T cells and simultaneously induces profound thymic atrophy.

We have recently demonstrated that the liver may be a major site of extrathymic T-cell differentiation. This hepatic pathway was shown to be activated in mice injected with heat-killed bacteria. It is conceivable that the resulting activation of macrophages or lymphocytes, and the production of cytokines may be responsible for a subsequent activation of hepatic T cells. In this context, we investigated the possibility of whether certain cytokines may activate hepatic T cells. It was demonstrated that the administration of lymphotoxin [tumour necrosis factor-beta (TNF-beta)] more than doubled the number of hepatic mononuclear cells (MNC) yielded 3-5 days after the treatment. More strikingly, such treatment induced profound thymic atrophy and resulted in a decrease of more than 95% in the number of thymocytes. Spontaneous proliferation in an in vitro culture of hepatic MNC from treated mice increased, and inversely such activity of thymocytes decreased. The increased number of hepatic MNC was mainly due to an increase in intermediate alpha beta T-cell receptor (TcR) cells, which are extrathymic T cells uniquely seen in the liver. On the other hand, the thymic atrophy was caused by the prompt apoptotic death of dull alpha beta TcR cells with double-positive (DP) CD4+ CD8+ phenotype. These results indicate that lymphotoxin may be one of the factors that activates extrathymic T cells in the liver and at the same time inhibits intrathymic T-cell differentiation.

Animals↗
PubMed1992

Ontogeny and development of extrathymic T cells in mouse liver.

We previously demonstrated that the liver may be a major site of extrathymic T-cell differentiation in mice. In the present study, the ontogeny and subsequent development of such T cells in the liver and other organs were investigated. This study was possible because these T cells have T-cell receptors (TcR) of intermediate intensity (i.e. intermediate TcR cells) and constitutively express a high level of interleukin-2 receptor beta chain (IL-2R beta). Therefore the two-colour staining for CD3 (or alpha beta TcR) and IL-2R beta identifies even a small proportion of intermediate TcR cells. The total numbers of mononuclear cells obtained from the liver, thymus and spleen varied from foetal to adult life. Especially in the liver, many haematopoietic cells were present in the parenchymal space at the foetal stage. There were no lymphocytes in the sinusoidal lumen at this period. In contrast, lymphocytes appeared in the hepatic sinusoids after birth and increased with ageing. Phenotypic analysis revealed that intermediate TcR cells appeared in the liver and spleen on Day 4 after birth. Bright TcR cells of thymic origin were also present in the peripheral organs on Day 4. Thereafter, intermediate TcR cells increased in the liver, whereas bright TcR cells increased in the periphery as a function of age. Similarly, thymectomized and congenitally athymic mice had mainly intermediate TcR cells in the liver and, to some extent, periphery. It is concluded that intermediate TcR cells, possibly of extrathymic origin, are generated only after birth and expand with ageing.

Aging↗
PubMed1991

Expansion of the population of double negative CD4-8- T alpha beta-cells in the liver is a common feature of autoimmune mice.

There have been several reports that double negative (DN) CD4-8- T alpha beta-cells might be responsible for the onset of autoimmune diseases in humans and mice. We previously revealed that such DN T alpha beta-cells are generated in the liver of autoimmune MRL-lpr/lpr mice. In the present study, we further characterize the histology of the liver in these mice by light and electron microscopic studies. An intensive accumulation of mononuclear cells in the liver was demonstrated and a significant proportion of these mononuclear lymphocytes was found to intimately interact with Kupffer cells or endothelial cells of the hepatic sinusoids. The majority of such lymphocytes were TcR+CD4-8-Pgp-1+ alpha beta-cells. Identification of DN T alpha beta-cells was then performed in various autoimmune model mice. Interestingly, all autoimmune mice tested (i.e., MRL-lpr/lpr, C3H/HeJ-gld/gld, BXSB, NOD, MRL(-)+/+ and NZB/W F1 mice), showed an increased proportion of DN T alpha beta-cells (greater than 11% among all MNC) in the liver when they became old and diseased. On the other hand, young and old normal mice and young autoimmune mice before the onset of disease did not have such a high proportion of DN T alpha beta-cells (less than 10%) in the liver. Among autoimmune mice, MRL-lpr/lpr and C3H/HeJ-gld/gld mice had lymphadenopathy, which consisted of DN T alpha beta-cells (greater than 25%), after the onset of disease. Autoimmune mice of the other strains had neither lymphadenopathy nor DN T alpha beta-cells in the periphery, even when they were diseased. These results suggest that the expansion of the DN T alpha beta-cell population in the liver is a common feature of autoimmune mice, irrespective of the information of lymphadenopathy.

Animals↗
PubMed1991

Reciprocal T cell responses in the liver and thymus of mice injected with syngeneic tumor cells.

We investigated the T cell responses in various tissues, especially in the liver and thymus, of mice injected with syngeneic tumors. This study was undertaken since recent evidence indicated that the liver is one of the important immune organs for T cell proliferation. When C3H/He mice were intraperitoneally injected with mitomycin-treated syngeneic MH134 tumors (1 x 10(7)/mouse), a transient increase of liver mononuclear cells (MNC) was induced, showing a peak at Day 4 after injection. Histological study of such liver showed a sinusoidal dilatation and an accumulation of MNC in the sinusoids. The most predominant MNC induced were double negative (CD4-8-) alpha beta T cells and gamma delta T cells. These gamma delta T cells varied, showing unique time-kinetics. Despite a continuous increase of whole liver MNC and alpha beta T cells, the proportion of gamma delta T cells in the liver decreased beginning 4 days after injection. In contrast with the response in the liver, a striking decrease in the cell number of thymocytes was induced after tumor injection, showing a basal level at Day 6. This hypocellularity in the thymus appears to be an inverted response of the lymphocytosis in the liver. At this time, a corresponding decrease in the proportion of double positive (CD4+8+) T cells was always seen in the thymus. Analysis of cell proliferative response showed that the increase of liver MNC after tumor injection was accompanied by augmented proliferation, whereas the decrease of thymocytes was accompanied by depressed proliferation. The present results indicate that there exists a unique, reciprocal response of T lymphocytes between the liver and thymus, and that the presence of tumor appears to stimulate T cell response in the liver but alternatively inactivates such response in the thymus.

Animals↗
PubMed1991

Unusual alpha beta-T cells expanded in autoimmune lpr mice are probably a counterpart of normal T cells in the liver.

Autoimmune MRL-lpr/lpr (lpr) mice develop severe lymphadenopathy, characterized by the accumulation of alpha beta-T cells with CD4-8- double negative (DN) phenotype, at the onset of disease. We previously demonstrated that the liver is a major site for the proliferation of such DN alpha beta-T cells. Herein, we further demonstrate that a large proportion of alpha beta-T cells in the liver and other organs, except the thymus, of lpr mice have unique properties, such as DN phenotype, relatively dull TCR intensity, a preponderance of V beta 8+ cells, and Pgp-1 expression. Interestingly, alpha beta-T cells in the liver of normal mice were found to consist of T cells with intermediate intensity of TCR (i.e., brighter than thymic dull TCR and lower than thymic bright TCR) as well as with bright intensity of TCR in the immunofluorescence test. These hepatic alpha beta-T cells with intermediate TCR in normal mice were found to have properties similar to those of alpha beta-T cells in lpr mice. These results suggest that abnormal alpha beta-T cells in lpr mice are a counterpart of normal T cells in the liver. An abnormal expansion of such T cells in the liver might be fundamental to the pathogenesis involved in these autoimmune mice.

Animals↗
PubMed1991

The appearance of T cells bearing self-reactive T cell receptor in the livers of mice injected with bacteria.

We demonstrated in the present study that with bacterial stimulation, an increased number of alpha/beta T cells proliferated in the liver of mice and that even T cells bearing self-reactive T cell receptor (TCR) (or forbidden T cell clones), as estimated by anti-V beta monoclonal antibodies in conjunction with immunofluorescence tests, appeared in the liver and, to some extent, in the periphery. The majority (greater than 80%) of forbidden clones induced had double-negative CD4-8-phenotype. In a syngeneic mixed lymphocyte reaction, these T cells appear to be self-reactive. Such forbidden clones and normal T cells in the liver showed a two-peak pattern of TCR expression, which consisted of alpha/beta TCR dull and bright positive cells, as seen in the thymus. A systematic analysis of TCR staining patterns in the various organs was then carried out. T cells from not only the thymus but also the liver had the two-peak pattern of alpha/beta TCR, whereas all of the other peripheral lymphoid organs had a single-peak pattern of TCR. However, T cells in the liver were not comprised of double-positive CD4+8+ cells, which predominantly reside in the thymus. The present results therefore suggest that T cell proliferation in the liver might reflect a major extrathymic pathway for T cell differentiation and that this hepatic pathway has the ability to produce T cells bearing self-reactive TCR under bacterial stimulation, probably due to the lack of a double-positive stage for negative selection.

Animals↗
PubMed1991

An appropriate in vitro culture condition for the induction of human TCR gamma delta + cells by heat-killed bacteria.

TCR gamma delta + cells proliferated when MNC were stimulated with various heat-killed bacteria. We investigated here the culture conditions for their maximum proliferation. MNC were cultured for 6 days with Streptococcus pyogenes, and for 3 days with T cell mitogens, PHA and anti-CD3 mAb, in medium supplemented with various concentrations (0.05-50%) of human sera. TCR gamma delta + and TCR gamma delta- CD2+3- double negative cells induced by Str. pyogenes required high concentrations of sera (greater than 6%) for their proliferation. Moreover, increased sera (up to 50%) greatly augmented their proliferation. On the other hand, TCR alpha beta + cell proliferation induced by T cell mitogens was supported by a small concentration (even 0.1%) of the sera, and the addition of high concentrations of sera (greater than 6%) somewhat suppressed responses. Similar serum requirement patterns were evident for the induction of cytotoxic cells. These results clearly demonstrated the existence of an appropriate culture condition for the proliferation of TCR gamma delta + cells induced in vitro.

Adult↗
PubMed1991

Further characterization of the autologous mixed lymphocyte reaction: induction of double negative gamma delta T lymphocytes.

To investigate the specific nature of the autologous mixed lymphocyte reaction (AMLR), we applied a method in which mixtures of NY-nonadherent responder cells and NY-adherent stimulator cells were treated with neuraminidase before culture and then cultured to assay the AMLR. This method produced a marked enhancement of DNA replication in the responder cells and the results were reproducible, regardless of the individuals tested. Using this method, we were able to make the following observations regarding the specific nature of the AMLR. (i) The AMLR is an IL-2-independent reaction, as revealed by bioassay to detect the presence of IL-2 by a blocking test using anti-IL-2R sera and as shown by the absence of mRNA for IL-2 in Northern hybridization. (ii) It is also HLA-DR dependent as proven by the fact that anti-DR sera almost completely inhibited the reaction. (iii) The AMLR was also found to induce the generation of activated CD4+ helper T cells in direct response to stimulation by NY-adherent cells, in which HLA-DR antigens were involved. (iv) Also, it induced the generation of CD4-CD8- double-negative (DN) lymphocytes, including gamma delta T cells with a cytotoxic activity against NK-resistant target cells and with a variety of lymphocyte activation markers (CD56, HLA-DR, CD25, transferrin receptors, CD38, and LFA-1). However, the AMLR did not induce the generation of NK cell markers CD16 and CD57. (v) The DN lymphocytes and gamma delta T cells appeared to be generated from the precursors of CD4-CD8- DN cells, in direct response to the stimulator cells. These results strongly suggest that the AMLR may be a phenomenon which induces the proliferative response of gamma delta T cells and their precursors, in addition to that of alpha beta T cells, particularly of CD4+ helper T cells.

Adult↗
PubMed1991

Predominant appearance of gamma/delta T lymphocytes in the liver of mice after birth.

gamma/delta T lymphocytes residing in the liver of mice were systematically characterized with respect to their age-related variation, phenotype and V gene segment usage of gamma/delta T cell receptor (TcR). Previous human and murine studies have shown that a high proportion of gamma/delta T cells reside in the liver and that such liver gamma/delta T cells have lymphoblastic morphology and can spontaneously proliferate in vitro. In the present study, a predominant appearance of gamma/delta T cells (up to 23% among CD3+ cells) in the liver was confirmed in 4-week old mice of various strains. gamma/delta T cells in the liver preferentially co-expressed CD8 antigens, whereas the vast majority of gamma/delta T cells in the spleen lacked the CD8 antigens. The identification of gamma/delta T cells in various lymphoid and non-lymphoid organs also revealed the liver to be one of the organs where gamma/delta T cell are most abundant. The level of such liver gamma/delta T cells showed a clear age-related variation. In the fetal stage and just after birth, gamma/delta T cells were not detectable in the liver (less than 0.2%). However, a significantly higher percentage of gamma/delta T cells among both the total population of mononuclear cells and CD3+ cells was detected in the liver of young 2- to 8-week-old mice; this percentage subsequently declined. As the total number of liver mononuclear cells increased in aged mice, the absolute number of liver gamma/delta T cells also increased as a function of age. V gene segment usage analysis by the polymerase chain reaction method demonstrated that V gamma 1 or V gamma 2/V delta 6 were preferentially used by liver gamma/delta T cells. The age-related increase of gamma/delta T cells was more prominent in the liver of athymic nude mice, and such gamma/delta T cells highly co-expressed the CD8 antigens and also utilized the V gamma 1 or V gamma 2/V delta 6 for gamma/delta Tcr. The predominant appearance of unique gamma/delta T cells in the liver, which was inversely related to the existence of the thymus, indicates that these gamma/delta T cells may differentiate extrathymically in the liver.

Age Factors↗
PubMed1991

Specific DNA binding of the TraM protein to the oriT region of plasmid R100.

The product of the traM gene of plasmid R100 was purified as the TraM-collagen-beta-galactosidase fusion protein (TraM*) by using a beta-galactosidase-specific affinity column, and the TraM portion of TraM* (TraM') was separated by collagenolysis. Both the TraM* and TraM' proteins were found to bind specifically to a broad region preceding the traM gene. This region (designated sbm) was located within the nonconserved region in oriT among conjugative plasmids related to R100. The region seems to contain four core binding sites (designated sbmA, sbmB, sbmC, and sbmD), each consisting of a similar number of nucleotides and including a homologous 15-bp sequence. This result, together with the observation that the TraM* protein was located in the membrane fraction, indicates the possibility that the TraM protein has a function in anchoring the oriT region of R100 at the sbm sites to the membrane pore, through which the single-stranded DNA is transferred to the recipient. sbmC and sbmD, each of which contained a characteristic inverted repeat sequence, overlapped with the promoter region for the traM gene. This suggests that the expression of the traM gene may be regulated by its own product.

Amino Acid Sequence↗
PubMed1991

Functional and molecular characteristics of acute lymphoblastic leukemia cells with a mature T-cell phenotype from a patient with ataxia telangiectasia.

A 12-year-old male patient with ataxia telangiectasia developed an acute lymphoblastic leukemia of T-cell phenotype. The lymphoblasts showed uniform surface expression of CD3, CD7, CD8, and T-cell receptor (TCR) alpha/beta chains, positive immunofluorescent staining of terminal deoxynucleotidyl transferase, complex cytogenetic aberrations including t(14;14) (q11;q32) and unique rearrangements of TCR beta and gamma chain genes, indicating the clonal expansion of leukemic cells. CD25 expression could be readily induced on the leukemic cells by mitogenic stimulation, followed by CD71 expression, but interleukin-2 production and subsequent proliferation in response to mitogens were subnormal.

Antigens, CD↗