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T Abo

Publications and source records attributed to T Abo.

At least 127 records · Page 7Linked to original sources

Therapeutic effects of glycyrrhizin in mice infected with LP-BM5 murine retrovirus and mechanisms involved in the prevention of disease progression.

Glycyrrhizin (GL), a plant extract, has been evaluated for its inhibitory effect on HIV replication in vitro and for its improvement of clinical symptoms in HIV-infected patients. In this study, we used GL in a murine AIDS model (MAIDS) to evaluate these effects. C57BL/6 mice were inoculated with LP-BM5 murine leukemia virus to cause MAIDS. Treatment with GL supplemented with glycine and cysteine (Stronger Neo-Minophagen C, SNMC) was then begun on day 0 or 4 wks after virus inoculation. SNMC was administered three times a week for up to 19 wks. Immunological abnormalities were monitored with respect to the surface phenotype identified by two-color staining for CD3 and IL-2 receptor beta-chain. All mice infected with the virus alone developed MAIDS and died by 14 wks after infection. The immunopathogenesis was estimated to be an abnormal expansion of intermediate CD3 cells (i.e., extrathymic T cells) as well as other types of lymphocytes. SNMC did not change the total mortality rate. However, some mice that began the treatment on day 0 or 4 wks after infection survived 3 wks longer. Splenomegaly and lymphadenopathy in such mice were suppressed. These mice showed normal phenotypic features and normal responses to Con A. These results suggest that SNMC is effective in some MAIDS mice in preventing the progression of disease. When lymphocytes isolated from the liver, spleen and lymph nodes of diseased mice were cultured in vitro, they showed a spontaneous proliferation. Interestingly, such proliferation was inhibited by addition of liver lymphocytes, but not splenic lymphocytes, obtained from normal or SNMC-treated mice. Since liver lymphocytes contains intermediate CD3 cells with autoreactivity, they may possibly suppress the progression of disease.

Animals↗

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↗

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↗

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↗

Increase in CD57 + CD16-lymphocytes in workers exposed to benzidine and beta-naphthylamine: assessment of natural killer cell subpopulations.

Previously, we found a decrease in CD4 + CD45RA + T lymphocytes in workers exposed to the aromatic amines (AAs) [benzidine (BZ) and beta naphthylamine (BNA)]. For further investigation of the effects of AAs on lymphocyte subpopulations, we measured natural killer (NK) cell subpopulations using two-color staining with anti-Leu7 (CD57) and anti-Leu11 (CD16) monoclonal antibodies in peripheral blood in 78 male dyestuff workers. The workers had been exposed to AAs before 1972 at a chemical plant, either in the production of AAs (40 workers, high-exposure group) or in other work that involved handling dyestuffs (38 workers, low-exposure group). The controls were 30 "healthy" male volunteers without a history of occupational exposure to AAs or hazardous chemicals. The number of CD57 + CD16- cells in the high-exposure group was significantly higher than that in the controls (P < 0.01, analysis of covariance with age as a covariate). No significant differences were found in CD57 + CD16-, CD57 + CD16+ and CD57- CD16 + NK cells between the low-exposure group and the controls. It is suggested that a decrease in the number of CD4+ T lymphocytes following exposure to AAs might be compensated by the increase in CD57 + CD16- cells, i.e. circulating peripheral lymphocytes with poor NK cell activity.

2-Naphthylamine↗

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↗

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↗

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↗

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↗

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↗

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↗

Adhesion molecules on intermediate TCR cells. II. Hepatoprotective effects of hyaluronic acid on acute liver injury.

The liver is a major organ wherein extrathymic T cells and NK cells exist in mice. Due to their unique properties, i.e., extrathymic T cells are TCR (or CD3)-intermediate+ IL-2R beta+ (herein termed intermediate TCR cells) and NK cells are TCR(-)IL-2R beta+, they are easily distinguished from the other lymphocyte subsets by using mAbs in conjunction with immunofluorescence tests. They were recently found to express a higher level of CD44 antigen, which is a ligand for hyaluronic acid, than that of another T cell subset (i.e., thymus-derived T cells or bright TCR cells). Since an intravenous administration of hyaluronic acid was also found to reduce the number of intermediate TCR cells and NK cells in the liver, we examined whether hyaluronic acid had a hepatoprotective effect on acute liver injury. Such injury was induced by LPS injection in mice pretreated with Propionibacterium acnes 1 week earlier. When a single dose of hyaluronic acid was given to these mice 12 hr before LPS injection, a prominent hepatoprotective effect was observed in terms of decreases of mortality (up to 50%), lymphocyte infiltration of the liver, serum transaminase levels, and tissue damage. At this time, liver mononuclear cells isolated from the treated mice showed decreased levels of cytokine production such as TNF and IL-1. These results reveal that intermediate TCR cells and NK cells in the liver actually adhere the sinusoid walls by means of an interaction of CD44 molecules and hyaluronic acid even in the case of acute liver injury. It suggests a possible therapeutic effect of the administration of hyaluronic acid in acute liver injury by eliminating the effector cells and cytokine-producing cells from the liver.

Adjuvants, Immunologic↗

Intermediate TCR cells with self-reactive clones are effector cells which induce syngeneic graft-versus-host disease in mice.

It has been established that, even after syngeneic bone marrow transplantation, animals treated with immunosuppressive drugs may suffer from graft-versus-host disease, showing autoimmune-like symptoms. Although the major effector cells are known to be T-cell subsets, detailed characterization of such T cells remains to be investigated. In the present study, we characterized them, especially as to whether they are thymus-derived T cells or extrathymic T cells, and how self-reactive clones were distributed among the above T-cell subsets. BALB/c mice (Mls-1b2a) were irradiated (9 Gy), subjected to bone marrow transplantation, and then treated with cyclosporin A (CsA) for 6 weeks. From 2 weeks after the cessation of CsA, these mice displayed signs of GVH disease. The major target organs included the liver and colon. Two-color staining for CD3 and IL-2R beta was applied to identify CD3-IL-2R beta+ NK cells, CD3-intermediate +IL-2R beta+ cells (i.e., intermediate CD3 or TCR cells of extrathymic origin) and CD3-high+IL-2R beta- cells (i.e., high CD3 cells of thymic origin). It was demonstrated that the major expanding lymphocytes were intermediate TCR cells and that self-reactive clones (V beta 3+ and V beta 11+ cells in this strain of mice) were confined to this population. Interestingly, these self-reactive clones had ability to respond to immobilized anti-V beta 3 and anti-V beta 11 mAbs. Liver MNC in mice with GVH disease which contained the highest proportion of intermediate TCR cells were able to mediate the adoptive transfer of GVH disease to other irradiated (6.5 Gy) mice. Intermediate TCR cells also showed potent cytotoxic activity against syngeneic leukemia cells. These results suggest that intermediate TCR cells are the major effector cells for the induction of syngeneic GVH disease.

Animals↗

Origin of CD57+ T cells which increase at tumour sites in patients with colorectal cancer.

Human T cells carrying natural killer (NK) markers, CD57 or CD56 antigens, appear to be distinguishable from other T cell subsets in terms of their granular lymphocyte morphology and their numerical increase in patients with AIDS and in recipients of bone marrow transplantation. At the beginning of this study, we observed that CD57+ T cells as well as CD56+ T cells were abundant at tumour sites in many patients with colorectal cancer. Since all these findings for CD57+ T cells are quite similar to those of extrathymic T cells seen in mice, we investigated how CD57+ T cells are distributed to various immune organs in humans. They were found to be present mainly in the bone marrow and liver, but to be completely absent in the thymus. Similar to the case of extrathymic T cells in mice, they were observed to consist of double-negative CD4-8- subsets as well as single-positive subsets (preponderance of CD8+ cells), and to contain a considerable proportion of gamma delta T cells. These features are striking when compared with those of CD57- T cells, which are characterized by an abundance of CD4+ subsets and alpha beta T cells. Not only at tumour sites but also in the peripheral blood, some patients with colorectal cancer displayed elevated levels of CD57+ cells. These results suggest that CD57+ T cells may be of extrathymic origin, possibly originating in the bone marrow and liver, and may be associated with tumour immunity, similar to another extrathymic population of CD56+ T cells in humans.

Adult↗

Androgen regulation of intra-and extra-thymic T cells and its effect on sex differences in the immune system.

Male predominance of malignant disease and female predominance of autoimmune diseases is widely known in humans. To elucidate one of the underlying mechanisms, we examined whether sex differences exist at the level of extra-thymic T cells in various organs of mice under physiological conditions. Effects of castration and testosterone administration were also examined. Intra- and extra-thymic T cells with T cell receptors (TCR) of bright and intermediate intensities, respectively, and with nil and high levels of the interleukin-2 receptor beta-chain respectively, were identified by immunofluorescence. Of the three strains tested, it was demonstrated that intermediate TCR cells were predominant in the liver of female mice. In the liver of male mice after bilateral orchidectomy, mononuclear cells increased and intermediate TCR cells predominated as if they were female; testosterone treatment prevented this immunological consequence of orchidectomy. As extra-thymic T cells comprise a considerable proportion of self-reactive forbidden clones and possess cytotoxic activity against syngeneic tumour cells, the present results suggest a possible relationship between (a) physiologically low levels of extra-thymic T cells in males and the male predominance of malignancy, and (b) the high levels of extra-thymic T cells in females and female predominance of autoimmune diseases.

Animals↗

Characterization of the functional sites in the oriT region involved in DNA transfer promoted by sex factor plasmid R100.

We have previously identified three sites, named sbi, ihfA, and sbyA, specifically recognized or bound by the TraI, IHF, and TraY proteins, respectively; these sites are involved in nicking at the origin of transfer, oriT, of plasmid R100. In the region next to these sites, there exists the sbm region, which consists of four sites, sbmA, sbmB, sbmC, and sbmD; this region is specifically bound by the TraM protein, which is required for DNA transfer. Between sbmB and sbmC in this region, there exists another IHF-binding site, ihfB. The region containing all of these sites is located in the proximity of the tra region and is referred to as the oriT region. To determine whether these sites are important for DNA transfer in vivo, we constructed plasmids with various mutations in the oriT region and tested their mobilization in the presence of R100-1, a transfer-proficient mutant of R100. Plasmids with either deletions in the sbi-ihfA-sbyA region or substitution mutations introduced into each specific site in this region were mobilized at a greatly reduced frequency, showing that all of these sites are essential for DNA transfer. By binding to ihfA, IHF, which is known to bend DNA, may be involved in the formation of a complex (which may be called oriT-some) consisting of TraI, IHF, and TraY that efficiently introduces a nick at oriT. Plasmids with either deletions in the sbm-ihfB region or substitution mutations introduced into each specific site in this region were mobilized at a reduced frequency, showing that this region is also important for DNA transfer. By binding to ihfB, IHF may also be involved in the formation of another complex (which may be called the TraM-IHF complex) consisting of TraM and IHF that ensures DNA transfer with a high level of efficiency. Several-base-pair insertions into the positions between sbyA and sbmA affected the frequency of transfer in a manner dependent upon the number of base pairs, indicating that the phasing between sbyA and sbmA is important. This in turn suggests that both oriT-some and the TraM-IHF complex should be in an appropriate position spatially to facilitate DNA transfer.

Base Sequence↗

Adhesion molecules on intermediate TCR cells. I. Unique expression of adhesion molecules, CD44+ L-selectin-, on intermediate TCR cells in the liver and the modulation of their adhesion by hyaluronic acid.

In addition to thymus-derived T cells, it was demonstrated recently that extrathymically differentiated T cells exist in the liver and other immune organs of mice. Since such extrathymic T cells have T-cell receptors (TCR) of intermediate intensity (i.e. intermediate TCR cells) and constitutively express IL-2 receptor beta-chain (IL-2R beta) similar to natural killer (NK) cells, they are easily distinguished from thymus-derived T cells with a TCR-bright+ IL-2R beta- phenotype (i.e. bright TCR cells). In the present study, the expression of adhesion molecules CD44 and L-selectin was compared between these T-cell subsets. Intermediate TCR cells in the liver and other organs were found to be CD44+ L-selectin- and, inversely, bright TCR cells were CD44- L-selectin+. CD3- IL-2R beta+ NK cells were also estimated to be CD44+ L-selectin-. Hyaluronic acid, which is known to adhere to a CD44 ligand, bound to intermediate TCR cells, but not to bright TCR cells. Among many extracellular matrices, hyaluronic acid induced a prominent decrease in the numbers and proportions of intermediate TCR cells and NK cells in the liver from 6 to 24 hr after in vivo administration. The half-life span of injected hyaluronic acid was approximately 7 hr in the plasma. These results suggest that the CD44 molecule, which is uniquely expressed on intermediate TCR cells and NK cells, is eventually associated with their adhesion to the sinusoidal walls in the liver.

Animals↗