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T Abo

Publications and source records attributed to T Abo.

At least 199 records · Page 11Linked to original sources
PubMed1990

Liver is a possible site for the proliferation of abnormal CD3+4-8- double-negative lymphocytes in autoimmune MRL-lpr/lpr mice.

MRL-lpr/lpr mice develop a severe autoimmune disease that resembles systemic lupus erythematosis in humans. The predominant immunological feature in these mice is the development of peripheral lymphadenopathy due to the expansion of an unusual T cell subset (TCR-alpha/beta +5CD3+4-8-B220+), which may be related to the onset of their autoimmunity. However, it is unknown whether such abnormal lymphocytes proliferate in the specific organs or not. We demonstrated in the present study that the number of liver nonparenchymal mononuclear cells (MNC) in the diseased MRL-lpr/lpr mice was 10 times greater than that of control MRL-+/+ mice. Moreover, the freshly isolated liver MNC of MRL-lpr/lpr mice vigorously proliferated in vitro and consisted of abnormal CD3+4-8- lymphocytes. Such in vitro proliferation was not observed in the MNC of other peripheral lymphoid organs. A potent natural cytotoxicity was also confined to the liver MNC in MRL-lpr/lpr mice. In vivo injection of [3H]TdR demonstrated that liver MNC incorporated [3H]TdR; such incorporation showed a peak on day 1, and the MNC-incorporated [3H]TdR appeared in the lymph nodes as late as day 5 after the injection. These results suggest that the liver is a possible site for the proliferation of abnormal lymphocytes, which may migrate thereafter into the peripheral organs in MRL-lpr/lpr mice.

Animals↗
PubMed1990

Induction of human TCR gamma delta + and TCR gamma delta-CD2+CD3- double negative lymphocytes by bacterial stimulation.

When human blood mononuclear cells (MNC) were incubated with heat-killed bacteria, proliferation of MNC was observed 5 days after stimulation, showing a peak on day 7. Interestingly, the bioassay of the culture supernatant and Northern blot analysis of mRNA demonstrated that no IL-2 production was associated with these proliferative responses. The induced lymphoblasts consisted predominantly of TCR gamma delta + (22.4 +/- 9.3%) and TCR gamma delta-CD2+CD3-(33.2 +/- 11.8%) double negative lymphocytes (n = 10), which were initially minor populations (less than 10%) in freshly isolated MNC. The prominent induction of TCR gamma delta + cells was confirmed by Northern blot analysis. TCR gamma delta + cells induced by bacterial stimulation seemed to generate from lymphocytes lacking the apparent expression of gamma delta TCR. The inducing capability for double negative cells is present in a large number of species of bacteria, especially Gram-positive bacteria. Gel filtration analysis of ultrasonicated filtrates of Staphylococcus aureus and Streptococcus pyogenes revealed that a substance with an Mr of 25-26 kd could be substituted for whole bacterial particles in the cell proliferative responses. In contrast to the purified protein derivative (PPD)-induced response, the response described here was inducible in the cord blood of neonates who had not yet been exposed to the corresponding bacterial infection. The physicochemical properties of the sonicated filtrates were different from those of PPD. These results suggested that the present phenomenon may be nonspecific, polyclonal (or oligoclonal) activation of TCR gamma delta + and TCR gamma delta -CD2+CD3- cells by bacterial stimulation.

Adult↗
PubMed1990

Identification of activated T cell receptor gamma delta lymphocytes in the liver of tumor-bearing hosts.

T cell receptor (TcR)gamma delta cells are known to be a minor population of T lymphocytes in the blood (less than 10%) and other peripheral lymphoid organs in healthy donors. We demonstrated here that a large proportion of TcR gamma delta cells, i.e., up to 30% of mononuclear cells (MNC) were detectable in the liver, but not other lymphoid organs of cancer patients. More importantly, the majority of such TcR gamma delta cells (greater than 70%) were shown to be lymphoblastic by electron microscopy. An activation marker of T lymphocytes, Leu-19 (CD56) was also highly expressed on the hepatic TcR gamma delta cells. The possibility of hepatic TcR gamma delta cells being activated was further examined in mice. C3H/He mice injected with syngeneic tumor cells were demonstrated to have an increased number of liver MNC; such MNC showed an ability to proliferate in vitro. These mice eventually had a considerable proportion of TcR gamma delta cells in the liver, showing activation markers, the Ia and LFA-1 antigens. These results suggest that the liver may be an important organ for activation and probably expansion of TcR gamma delta cells especially in tumor bearing hosts.

Animals↗
PubMed1990

[Gamma delta TCR cells in hepatic sinusoids and intestinal intraepithelia].

We provided here the conception that the liver is an important immune organ after birth. On the other hard, it is well established that the liver in the fetal stage works as a hematopoietic organ. Although a significant number of gamma delta TCR cells are distributed in epithelia of the skin, intestine and reproductive organs, the liver is also one of the most predominant organs of gamma delta TCR cells. The percentages of gamma delta TCR cells in MNC of hepatic sinusoids increased up to 16.0% in young mice aged 4 wk, and approximately 40% of such gamma delta TCR cells expressed the CD8 antigens. V gene segment usage analysis by the PCR method demonstrated that a unique set of V gamma 2/V delta 6 was preferentially used by hepatic gamma delta TCR cells. The predominant appearance of unique gamma delta TCR cells in hepatic sinusoids of mice, including nude mice, proposed us the possibility that these gamma delta TCR cells may differentiate non-thymus dependently in the liver. The lymphocytes in the hepatic sinusoids may be intimately related to the antigens come from the intestine and to the lymphocytes sensitized there. Therefore, we introduced recent evidences about gamma delta T cells in the intestine and discussed their connection with the hepatic gamma delta T cells.

Animals↗
PubMed1989

Analysis of mechanisms by which NK cells acquire increased cytotoxicity against class I MHC-eliminated targets.

Acid treatment, where cells are exposed to 0.2 M citric acid buffer at pH 3 for 2 min, was described in a previous paper to be a method which specifically eliminates class I MHC antigens from the membrane of viable cells. We applied this method to characterize functional roles of class I MHC antigens on the target cells in NK cell cytotoxicity. When NK target cells, U937, Molt-4, and Raji, were subjected to acid treatment, the treated cells lost their surface class I MHC antigens and became more sensitive to NK cell killing. On the other hand, the susceptibility of K562 cells which initially lacked class I MHC antigens did not significantly change after such treatment. We then examined the mechanism which enables NK cells to become more cytotoxic against class I MHC antigen-eliminated target cells. Single cell binding assay and cold target inhibition assay demonstrated that class I MHC antigen-eliminated target cells did not acquire high binding affinity to NK cells. However, the interaction between NK cells and class I MHC antigen-eliminated targets resulted in a greater increase in production of NKCF-like factor than did the interaction between NK cells and untreated targets. Class I MHC antigen-eliminated targets did not acquire high killer susceptibility to NKCF-like factor. The present study utilizing the acid treatment method confirmed that surface class I MHC antigens on the targets are important immunoregulatory molecules not only for cytotoxic T lymphocytes but also for NK cells and elucidated some of the underlying mechanisms.

Acids↗
PubMed1989

Recombinant human tumor necrosis factor alpha suppresses autoimmune diabetes in nonobese diabetic mice.

We previously reported that administration of a streptococcal preparation (OK-432) inhibited insulitis and development of autoimmune diabetes in nonobese diabetic (NOD) mice and BB rats as animals models of insulin-dependent diabetes mellitus. In this study, we screened various cytokines that could be induced by OK-432 in vivo, for their preventive effect against diabetes in NOD mice. Among recombinant mouse IFN gamma, human IL1 alpha, human IL2, mouse granulocyte-macrophage colony-stimulating factor and human TNF alpha, only human TNF alpha suppressed insulitis and significantly (P less than 0.001) inhibited development of diabetes. NOD mice were the lowest producers of the mRNA of TNF and serum TNF on stimulation with OK-432 or with IFN gamma plus LPS, compared with C57BL/6, C3H/He, and Balb/c mice. The results imply a role for low productivity of TNF in the pathogenesis of autoimmune diabetes in NOD mice.

Animals↗
PubMed1989

[Histopathological and clinical studies of acute necrotizing ulcerative gingivitis and evaluation of treatment].

We report the clinical data, light and electron microscopic findings, therapy and clinical course of three cases treated for acute necrotizing ulcerative gingivitis. The following results were obtained. 1. An ulcerous lesion was observed in the gingiva of all three cases, with case I also showing a depressed lesion in the ulcerous region. 2. In all three cases, the gingival sections displayed ulceration and showed fibrin deposition and neutrophil infiltration on the surface of the ulcerous region. Congested blood vessels and neutrophil infiltration also were observed in the connective tissue beneath the ulcerous region. 3. Many microorganisms, fibrin, cell debris, and enlarged intercellular spaces of the epithelium were seen on the surface on the ulcerous region. 4. Localized treatment, mainly plaque control, was found to be effective clinically and histopathologically.

Gingivitis, Necrotizing Ulcerative↗
PubMed1989

Epidermodysplasia verruciformis accompanied by large granular lymphocytosis. Report of a case and immunological studies.

A 34-year-old man with epidermodysplasia verruciformis showed increased natural killer (NK) cell activity in his peripheral blood cells, which was found to be due to abnormal expansion of large granular lymphocytes (LGL). Surface marker analysis of LGL in a two-color immunofluorescence test demonstrated that all LGL subsets, Leu-7+11-, Leu-7+11+, and Leu-7-11+, were increased. In contrast, his peripheral blood mononuclear cells showed a remarkable decrease in response to T cell mitogens, which could not be restored by depletion of the LGL subpopulation from the mononuclear cells. Immunohistologic studies for dermal distribution of LGL showed numerous Leu-7+ cells but no Leu-11+ cells at the sites of delayed hypersensitivity reaction or interferon beta- or interferon gamma-injected sites. These findings suggest that the elevated NK cell activity in this patient with epidermodysplasia verruciformis was caused by overall expansion of normal LGL subpopulations, but that the decreased T-cell mitogenic response represented a primary T-cell defect rather than a direct suppression by increased NK cells. It is noteworthy that despite this extraordinary increase of all LGL subpopulations in the blood, Leu-11+ NK cells never appeared in the skin.

Adult↗
PubMed1989

[Identification and characterization of effector lymphocytes lysing autologous tumor cells].

Effector lymphocytes cytotoxic to autologous tumor cells consist of heterogeneous populations. In this communication, we have presented the results of experiments, in which these heterogeneous effector cells were classified based on their surface markers and modes of differentiation depending upon culture conditions. NK cells with a typical phenotype of CD2+ 3-16+ were one of major populations, which could respond to IL-2 and be differentiated into lymphokine activated killer (LAK) cells. LAK cells were also induced from a CD3+4-8- T cell subset by IL-2 stimulation. Effector cells with a phenotype of CD2+ 3-4-8-16-, which may belong to the T cells at early stages of differentiation, could also be induced by stimulation of immunoadjuvants. Finally, it was shown that the effector cells with a typical phenotype of cytotoxic T lymphocytes, CD3+4-8+16-, and a non-MHC-restricted cytotoxicity were induced by IL-2 in the tumor infiltrating lymphocytes.

Adjuvants, Immunologic↗
PubMed1988

Age-related variation in the proportion and activity of murine liver natural killer cells and their cytotoxicity against regenerating hepatocytes.

We investigated the distribution of liver NK cells in mice of various ages and their cytotoxicity against regenerating hepatocytes. Liver NK cells were identified by asialo GM1 antibody in mononuclear cell suspension from the liver, whereas NK activity was assayed against YAC-1 target cells. Mononuclear cells in the liver consisted of more than 25% NK cells with potent NK activity in C3H/He mice, 8 wk of age. The strain-specific distribution (C3H/He greater than C57BL/6 greater than DBA/2) of liver NK cells was the same as those in the spleen and blood. The proportion of liver NK cells and the level of NK activity in C3H/He mice were further demonstrated to vary depending on age, in that both the proportion and the function were generated at 4 wk of age, reached a maximum between the 6th and 8th wk, and then rapidly decreased around the 9th wk. The appearance of an increased number of NK cells in the liver seemed to coincide with the slowing of the rapid increase of murine liver weight. We then investigated whether liver NK cells mediated their cytotoxicity against regenerating hepatocytes. Both specific 51Cr-release assay and single cell cytotoxicity assay demonstrated that liver NK cells were significantly cytotoxic against regenerating hepatocytes in partially hepatectomized liver, but to a lesser extent against normal hepatocytes in resting liver. Morphologic study revealed that normal liver predominantly consisted of hepatocytes with binuclei (greater than 60%) but that regenerating liver mainly consisted of hepatocytes with a single nucleus (greater than 70%). One-nucleus hepatocytes were more susceptible to the cytotoxicity of liver NK cells. A comparative study of restoration kinetics of the liver weight and the number of liver NK cells after partial hepatectomy also showed a unique relationship. These results raise the possibility that liver NK cells might be responsible for regulating hepatocyte growth.

Aging↗
PubMed1988

Prerequisite for the induction of lymphokine-activated killer cells from T lymphocytes.

Human blood mononuclear cells were separated into Leu-11+7-NK, Leu-11-7+, and Leu-11-7-T cells by means of a combination of the Percoll gradient method and C-mediated cytolysis using mAb. When purified Leu-11+7-NK, Leu-11-7+, and Leu-11-7-T cells were cultured with rIL 2 (500 U/ml) for 6 days in a medium supplemented with 10% FCS, Leu-11+7-NK cells responded at the maximum level and Leu-11-7+ cells responded moderately as shown by both cell-proliferation response and cytotoxic activity generated. On the other hand, Leu-11-7-T cells did not respond at all to rIL-2. However, when Leu-11-7-T cells were cultured with rIL-2 in a medium supplemented with 10% autologous serum, they showed considerable responsiveness to rIL-2. In addition, much greater response to Leu-11-7-T cells were produced by the addition of monocytes. Monocyte cytokines, neither IL 1, IFN-gamma, TNF, nor their combination were able to substitute for monocytes in the induction culture. In contrast, the response level of Leu-11+7- NK cells remained unchanged irrespective of supplementation with autologous serum to medium or the addition of monocytes to the culture. These results indicated that culture conditions in the experiments significantly affected the results as to determination of lymphokine-activated killer cell precursors, especially the result pertaining to the conversion of T lymphocytes to lymphokine-activated killer cells. Under appropriate conditions, not only NK cells but also T cells are important precursors of lymphokine-activated killer cells.

Adult↗
PubMed1988

Cytokines produced by blood mononuclear cells stimulated with the streptococcal preparation OK-432: effect on production by supplementing the medium with xenogeneic serum.

Human blood MNC were stimulated for 7 days with a streptococcal preparation, OK-432, in a medium supplemented with either 10% autologous serum (autoserum) or 10% FCS. Cytokines, including IL-2, IL-1, IFN, and TNF in the supernatants, and antitumor cytotoxicity of MNC were analyzed. None of the IL-2 was detectable during the culture in medium with autoserum, although significant enhancement of cytotoxicity was observed at day 1. On the other hand, production of IL-2 and higher cytotoxicity were induced in the medium with FCS. Even a control culture of MNC unstimulated with OK-432 in the medium with FCS, showed a slight but significant amount of IL-2 and considerable cytotoxicity. However, such a culture in the medium with autoserum showed no such IL-2 production or cytotoxicity. The cytotoxicity induced in the medium with FCS was significantly inhibited by the addition of anti-IL-2 antibody to the culture as well as by the addition of anti-IFN gamma antibody, whereas the cytotoxicity in the medium with autoserum was not inhibited at all by anti-IL-2 antibody. Therefore, the cytotoxicity induced in the medium with FCS included IL-2-induced killer activity, i.e., LAK activity. Similarly, the levels of IL-1, IFN, and TNF production in the supernatants were variable depending on the serum used to supplement the medium. The nonspecific production of IL-2 and the unexpected induction of cytotoxicity were consistently provoked in the medium using several different lots of FCS, but not in the medium with human allogeneic sera or pooled AB serum nor in that with autoserum. It was revealed that the source of sera used to supplement the medium is an important factor affecting the results of analysis of cytokine production and cytotoxicity of MNC induced by certain stimulants.

Adult↗
PubMed1987

A simple method to eliminate the antigenicity of surface class I MHC molecules from the membrane of viable cells by acid treatment at pH 3.

We describe here a simple, reproducible method which specifically eliminates the antigenicity of surface class I major histocompatibility complex (MHC) molecules by acid treatment at pH 3 from the membrane of viable cells. When fresh mononuclear cells (MNC) or established cultured cell lines were treated at 4 degrees C for 2 min with citric acid buffer at pH 3 containing 1% bovine serum albumin, the antigenicity of class I MHC molecules, but not those of class II MHC and the other non-MHC antigens, was eliminated from the surface membrane without significant cell death. This method was effective for both human and murine cells with various origins. Monoclonal and polyclonal antibodies were used to identify the expression of surface antigens in conjunction with immunofluorescence tests. The eliminated antigenicity of human class I MHC antigens (i.e., HLA-A,B,C) on MNC regenerated when cells were incubated in the medium at 37 degrees C for 10 h. The pretreatment of cells with emetine (10(-4) M), a protein synthesis inhibitor, was found to be effective in inhibiting this regeneration. The acid treatment method might be useful for future studies on the functional characterization of surface class I MHC antigens.

Animals↗
PubMed1987

Increased production of tumor necrosis factor and prostaglandin E2 by monocytes in cancer patients and its unique modulation by their plasma.

We investigated the role of monocytes in the production of tumor necrosis factor (TNF) and prostaglandin E2 (PGE2) in 77 cancer patients with malignancies of the digestive tract, using 30 normal individuals and 18 noncancer patients as controls. Monocytes were incubated with lipopolysaccharide for 20 h, and TNF production and PGE2 production were analyzed by bioassays. Elevated levels of TNF (greater than 512 U/ml) and PGE2 (greater than 8 ng/ml) production were demonstrated in many cancer patients when these factors were induced in the medium with 10% fetal bovine serum. The elevated level of TNF was seen to be restricted for the most part to patients with malignancies. Thus, 51 out of 59 cancer patients (86%), consisting of 44 primary cancer patients and 15 recurrent cancer patients, showed an increased level of TNF. In contrast, almost all of 18 postoperative cancer patients showed TNF levels comparable to those of normal individuals. Furthermore, 16 primary cancer patients were also demonstrated to have reduced levels of TNF production by monocytes after curative operation. When 10% cancer-patient plasma was added to the induction culture, TNF production by monocytes was drastically suppressed in the cancer patients. Interestingly, the same addition of plasma induced a prominent enhancement of PGE2 production in the cancer patients. The plasma of noncancer patients did not modulate production of these factors. No TNF activity was found in the plasma of cancer patients, but such plasma did contain an increased level of PGE2 (100-300 pg/ml). Although PGE2 (greater than 2 ng/ml) was able to suppress TNF production by monocytes, the addition of 10% plasma PGE2 was not enough to induce suppression. An unknown factor(s) in the plasma of cancer patients may uniquely modulate the elevated TNF and PGE2 production in these patients.

Adolescent↗
PubMed1987

Enhancement of human natural killer activity by the monoclonal Leu-11 antibodies.

The Fc receptor for IgG on human natural killer (NK) cells can be identified by a series of murine monoclonal antibodies. When these antibodies with IgG1 isotype (e.g., Leu-11a and Leu-11c), but not with IgM (e.g., Leu-11b and VEP13), were added to NK assay culture against K562 targets of 4-hr analysis, a considerable enhancement of NK activity was induced. An enhancement was shown at a concentration of up to 10(-5) mg/ml of Leu-11a. Furthermore, the present experiments demonstrated that many established cell lines with diverse cell origins expressed the Leu-11 antigens, and enhancement of NK activity by Leu-11 was induced when these Leu-11+ cell lines were used as targets in NK assays. The results that Leu-11a caused an increase in effector-to-target cell conjugates, and that F(ab')2 of Leu-11a was effective in enhancement of NK activity, but the Fab was not, indicated that Leu-11 might become a linkage between the effector and target cells. Significance of this phenomenon was discussed regarding practical application of Leu-11 antibodies in laboratory experiments and in clinical studies.

Antibodies, Monoclonal↗
PubMed1987

[Experimental study on the control of cisplatin-induced emesis in dogs].

In order to search for methods of controlling cisplatin-induced emesis, a series of experiments were performed with dogs. Cisplatin was administered i.v. to dogs at three-day intervals, and the number of emetic episodes and latency period to the first episode following injection were examined. The dose of cisplatin was 0.3mg/kg at the first injection, and thereafter square root 2-fold higher doses than the preceding ones were injected up to a maximum of 2.4 mg/kg. Emesis was observed from 0.42 g/kg. The number of emetic episodes increased with escalation of the dose up to 0.85 mg/kg, but decreased at higher doses. On the other hand, the latency period shortened with increase of the dose up to the highest one. From these results, the latency period is concluded to be a reliable parameter for evaluating the emetic activity of cisplatin and the efficacy of anti-emetics. The anti-emetic effect of vagotomy, ethyl amino-benzoate or metoclopramide was then examined. When 1 mg/kg of cisplatin was administered i.v., mean values of latency period and the number of episodes in dogs of a control group were 200 minutes and 20 times, respectively. In vagotomized dogs, no emesis was observed. When ethyl amino-benzoate was administered p.o. at doses of 12, 24 and 48 mg/kg 30 minutes before and 90 minutes after cisplatin injection, the number of episodes decreased to between 8 and 4.3 times, but the latency period was not prolonged. When s.c. injections of 1 mg/kg metoclopramide were combined with cisplatin in a similar manner to ethyl amino-benzoate, the latency period was prolonged up to 343 minutes, and the number of episodes decreased to 2.7 times. These results suggest that the peripheral autonomic nervous system is involved in the mechanism of emesis induction by cisplatin. Finally, the anti-emetic effect of metoclopramide was examined using the following administration schedules of cisplatin: a single i.v. injection of 3.75 mg/kg and daily i.v. injections of 1.25 mg/kg for three days. Metoclopramide showed a superior anti-emetic effect in the latter schedule, when the dose of 2 mg/kg was given i.v. 30 minutes before and 90 and 210 minutes after the cisplatin injection.

Analysis of Variance↗