Biomedical subjects

H Hiraide

Publications and source records attributed to H Hiraide.

At least 19 recordsLinked to original sources

PubMed2006

Multiple interleukin-18 injections promote both mouse Th1 and Th2 responses after sublethal Escherichia coli infection.

Interleukin (IL)-18 is considered to induce exclusively the Th1 immune response but not the Th2 response in the presence of adequate IL-12 stimulation in bacterial infections. However, we demonstrate herein that multiple IL-18 injections to the mice not only enhance the early Th1 response but also stimulate the Th2 response later after viable Escherichia coli infection. Multiple IL-18 injections (three alternate-day injections) raised the serum interferon (IFN)-gamma level at 6 h and serum Th2 cytokine levels, such as IL-4, IL-10 and IL-13, at 48 h after infection, while a single IL-18 injection increased only the serum IFN-gamma level. Depletion of mouse CD4+ cells suppressed the IL-18-induced Th2 cytokines, IL-4, IL-10 and IL-13. In contrast, depletion of natural killer (NK)1.1+ cells reduced the IFN-gamma and IL-13 levels. Moreover, multiple IL-18 injections up-regulated the serum IgM level at 72 h after infection while a single IL-18 injection did not. Interestingly, neutralization of IL-4 but not IFN-gamma partially suppressed the increased serum IgM. Liver mononuclear cells (MNCs) from the mice treated with multiple IL-18 injections significantly increased more production of not only IFN-gamma but also Th2 cytokines and IgM by in vitro lipopolysaccharide (LPS) stimulation than those from the phosphate-buffered saline (PBS)-treated mice, while liver MNCs from the single IL-18-injected mice also increased IFN-gamma production but significantly suppressed IL-4 and IgM production compared to those from the PBS-treated mice. Our findings suggest that multiple injections of IL-18 up-regulate both the cellular and humoral innate immunities, thereby enhancing host defence against bacterial infections.

Animals↗

PubMed2003

Characterization of bronchoalveolar lavage T cell subsets in sarcoidosis on the basis of CD57, CD4 and CD8.

T cells expressing CD57 (a natural killer cell marker) with interferon-gamma (IFN-gamma) producing capacity increase under various conditions. CD57+ T cells are also present in the bronchoalveolar lavage fluid (BALF) of sarcoidosis, and several phenotypical and functional analyses of these cells have been reported. In the present study, BALF T cells obtained from 52 patients with sarcoidosis were classified further into CD4+CD57+ T cells, CD4+CD57- T cells, CD8+CD57+ T cells and CD8+CD57- T cells and their phenotypes and functional characteristics were assessed. Substantial proportions of these T cell subsets expressed natural killer cell markers CD161 and CD122. The biased expansion of Vbeta2 T cells was observed in both CD4+CD57+ T cells and CD4+CD57- T cells in BALF from most patients, while the expansion of other Vbeta T cells was also observed in some patients. Unexpectedly, the biased expansion of certain Vbeta T cells was also seen in either CD8+CD57+ T cells or CD8+CD57- T cells, while the expanded Vbeta T cells in CD8+ T cells differed substantially among individuals. BALF T cells showed a remarkably lower T cell receptor (TCR) intensity than that of peripheral blood T cells. Both CD8+ T cell subsets in BALF of sarcoidosis expressed the intracellular perforin/granzyme B, while all four subsets expressed intracellular IFN-gamma after in vitro activation, and CD4+ T cells, especially CD4+CD57+ T cells, expressed tumour necrosis factor-alpha. These findings indicate that CD57+ T cells as well as CD57- T cells in the BALF are phenotypically and functionally different from peripheral blood T cells and may play an important role in the Th1 dominant state and inflammation in pulmonary sarcoidosis.

Antigens, CD↗

PubMed2002

Activation of human T cells with NK cell markers by staphylococcal enterotoxin A via IL-12 but not via IL-18.

We have reported recently that mouse liver NK cells and NK1 x 1+ T cells were activated by bacterial superantigens via the IL-12 production from Kupffer cells. In the present study, we examined the effect of staphyloccoccal enterotoxin A (SEA) on human T cells with NK cell markers, CD56 or CD57 (NK-type T cells). After stimulating peripheral blood mononuclear cells (PBMC) with SEA, PBMC produced a large amount of IFN- and acquired a potent antitumour cytotoxicity. The in vitro depletion of either CD56+ TCR NK cells, CD56+ T cells or 57+ T cells from PBMC significantly inhibited the IFN- production from PBMC. When purified NK-type T cells, NK cells and regular T cells were cultured with monocytes and SEA they all produced IFN-, while the IFN- amounts produced by both NK-type T cells were greater than those produced by NK cells. NK cells as well as CD56+ T cells showed cytotoxicity against NK-sensitive K562 cells, whereas both NK-type T cells showed a more potent cytotoxicity against NK-resistant Raji cells than did NK cells. The IFN- production from each population as well as from whole PBMC was greatly inhibited by anti-IL-12 antibody but not by anti-IL-18 antibody. The antitumour cytotoxicity of whole PBMC was also significantly inhibited by anti-IL-12 antibody while the SEA-induced proliferation of PBMC was not affected by anti-IL-12 antibody. Furthermore, SEA-activated NK-type T cells as well as NK cells showed cytotoxicities against vascular endothelial cells. Our findings suggest that human NK-type T cells are thus involved in bacterial superantigen-induced immune response.

Biomarkers↗

PubMed2002

CD57+ T cells augment IFN-gamma production in a one-way mixed lymphocyte reaction and their expansion after stem cell transplantation in paediatric patients.

To clarify the immune response of CD57+ T cells (most of them are CD8+) in peripheral blood (PB) against alloantigens in order to elucidate the T helper 1 (Th 1) immune response, we assessed the role of CD57+ T cells in IFN-gamma (one of the representative Th 1 cytokines) production in a one-way mixed lymphocyte reaction (MLR). In this study, we showed that CD57+ T cells in responder cells were essential for effective IFN-gamma production in allogeneic MLR due partly to the augmentation of the alloresponse of regular T cells. Furthermore, IFN-gamma production in MLR correlated with the proportions of CD57+ T cells in PB regardless of the responders' age. We also showed that the extent of the expansion of CD57+ T cells in paediatric patients after haematopoietic stem cell transplantation (HSCT) was markedly lower than that in adult patients. In addition, CD57+ T cells purified and activated with a combination of cytokines showed a greater cytotoxicity than regular T cells against human umbilical vein endothelial cells. Because IFN-gamma production in one-way MLR is a useful predictor of graft-versus-host disease (GVHD), especially in the acute phase that occurs after allogeneic HSCT, our findings suggested that CD57+ T cells play a role in the development of GVHD and thus may explain the reason as to why a higher donor age is associated with an increased risk of developing GVHD while, in addition, the incidence of severe GVHD in paediatric patients is lower than that in adult patients.

Adult↗

PubMed2001

Preoperative serum interleukin-18 level as a postoperative prognostic marker in patients with gastric carcinoma.

BACKGROUND: Interleukin-18 (IL-18), a recently described cytokine produced mainly by macrophages, stimulates interferon-gamma (IFN-gamma) production by natural killer cells and T cells. Although it has been reported that serum IL-18 levels are higher in patients with advanced tuberculosis and acute graft-versus-host disease compared with normal controls, the authors found no reports regarding serum IL-18 levels in patients with malignant solid tumors. The purpose of this study was to determine serum IL-18 levels and their clinical significance in patients with gastric carcinoma. METHODS: Peripheral blood samples were obtained from 94 patients with gastric carcinoma who underwent curative surgery and from 50 healthy volunteers. The serum IL-18 level, the IFN-gamma, level, and the Helicobacter pylori (HP) serology status were determined in each sample with an enzyme-linked immunosorbent assay. RESULTS: The mean serum IL-18 level for all patients was significantly higher compared with the mean level in healthy volunteers (P < 0.01). IFN-gamma titers were below the level of detection in all samples tested. When the patients were subdivided into groups, it was found that the serum IL-18 level in patients with Stage II and III disease was significantly higher compared with the level found in healthy volunteers (P < 0.01). The serum IL-18 level decreased after patients underwent surgical resection. However, there was no significant difference in the serum IL-18 level between healthy controls and patients with Stage I or IV disease. Patients with IL-18 levels >or= 310 pg/mL (i.e., equal to or greater than the mean levels +/- 1 standard deviation in the healthy volunteers) experienced a significantly lower survival rate compared with patients who had IL-18 levels < 310 pg/mL after undergoing surgery (P < 0.05) despite a lack of any discernible difference in clinicopathologic factors between the two groups. The serum IL-18 level was identified as an independent postoperative prognostic factor in multivariate survival analysis using a Cox proportional hazards model (hazard ratio, 4.89; P = 0.01). There was no significant correlation between HP serology status and serum IL-18 levels. CONCLUSIONS: The preoperative serum IL-18 level may represent a significant postoperative prognostic determinant in patients with gastric carcinoma. Its function in the host immune system remains to be elucidated.

Aged↗

PubMed2001

The mechanism of a defective IFN-gamma response to bacterial toxins in an atopic dermatitis model, NC/Nga mice, and the therapeutic effect of IFN-gamma, IL-12, or IL-18 on dermatitis.

NC/Nga (NC) mice raised under conventional conditions (Conv. NC mice) spontaneously develop dermatitis similar to human atopic dermatitis, whereas NC mice raised under the specific pathogen-free conditions do not develop dermatitis. In the present study, we show that the representative Th1 cytokine, IFN-gamma levels in the sera of NC mice, injected with either staphylococcal enterotoxin B or endotoxin (LPS), to be severalfold lower than those of normal mice. The low IFN-gamma response to staphylococcal enterotoxin B was correlated to the lack of regular Vbeta8(+) T cells and Vbeta8(+) NK T cells, and the low IFN-gamma response to LPS was correlated to an impaired IL-18 production of macrophages. The CD3-stimulated IL-4 production from liver and spleen T cells from Conv. NC mice in vitro was greatly augmented. The serum IL-4 levels of untreated Conv. NC mice also were higher than those of normal mice and specific pathogen-free NC mice. Treatment of Conv. NC mice either with IFN-gamma, IL-12, or IL-18 twice a week from 4 wk of age substantially inhibited the elevation of the serum IgE levels, serum IL-4 levels, and dermatitis, and IL-12 or IL-18 treatment also reduced the in vitro IL-4 production from CD3-stimulated liver T cells. The systemic deficiency in the Th1 response to bacterial stimulation thus leads to a Th2-dominant state and may induce an abnormal cellular immune response in the skin accompanied with an overproduction of IgE and a susceptibility to dermatitis in NC mice.

Adjuvants, Immunologic↗

PubMed2001

Interleukin-10 and interferon-gamma levels within the peritoneal cavity of patients with gastric cancer.

BACKGROUND AND OBJECTIVES: Immune status in the peritoneal cavity of patients with gastric cancer remains largely unknown. To clarify the clinical significance of the host immune response within the peritoneal cavity, we examined the levels of interferon-gamma (IFN-gamma), a type 1 cytokine, and interleukin-10 (IL-10), a type 2 cytokine, in peritoneal washings obtained from patients with gastric cancer. METHODS: Both the concentrations of IFN-gamma and of IL-10 in peritoneal washings obtained during surgery from 56 patients with gastric cancer were determined by an enzyme-linked immunosorbent assay. RESULTS: The IFN-gamma level was not correlated with the IL-10 level. The IL-10 level increased in a stage-dependent manner. The high IL-10 level correlated with an unfavorable outcome, whereas there was no relationship between the IFN-gamma level and survival rate. However, among the stage III-IV cancer patients, the high IFN-gamma level correlated with a favorable outcome, while there was no relationship between the IL-10 level and survival rate. CONCLUSION: Although the IL-10 level increases with tumor progression, the outcome of patients with advanced gastric cancer may be affected by the IFN-gamma level, but not by the IL-10 level, in the peritoneal cavity.

Adult↗

PubMed2001

5'-deoxy-5-fluorouridine, medroxyprogestrone acetate and mitoxantrone hydrochloride for advanced or recurrent breast cancer.

BACKGROUND: In treating advanced or recurrent breast cancer, anthracycline-containing chemotherapy is used for palliation and to maintain quality of life. However, there are several drawbacks including therapeutic failure and cardiotoxicity. We evaluated the efficacy and toxicity of combination chemotherapy with 5'-deoxy-5-fluorouridine (5'-DFUR), medroxyprogestrone acetate (MPA) and mitoxantrone hydrochloride (MIT). METHODS: Sixteen patients with advanced or recurrent breast cancer were enrolled. Chemotherapy was given in a 28-day cycle, starting with MIT 10 mg/m2 intravenously on day 1, then oral 5'-DFUR 800 mg and MPA 800 mg daily. Two or more cycles were given. RESULTS: Fifteen patients were assessable for response and toxicity. Thirteen patients had been treated previously with an anthracycline containing regimen and 2 with CMF. There were 2 partial response patients (13.3%) and 1 complete response patient (6.7%). There were 11 patients showing no change (NC) (73.3%), one of whom was a minor responder and 7 with a long period of NC. There was only one with progressive disease patient. The overall response rate was 20.0%. Adverse events occurred in 5 patients (33.3%). Myelosuppression was the most common with 5 patients becoming leukopenic (33.3%). Nausea/vomiting was the second most common side effect, affecting 2 patients (13.3%). CONCLUSION: Given its high efficacy and preservation of QOL, the combination of MIT, 5'-DFUR and MPA can be a 2nd or 3rd line therapy for advanced or recurrent breast cancer, especially for anthracycline-resistant cases.

Adult↗

PubMed2001

Systematic characterization of human CD8+ T cells with natural killer cell markers in comparison with natural killer cells and normal CD8+ T cells.

We investigated the function of CD56+ CD8+ T cells (CD56+ T cells) and CD56- CD57+ CD8+ T cells (CD57+ T cells; natural killer (NK)-type T cells) and compared them with those of normal CD56- CD57- CD8+ T cells (CD8+ T cells) and CD56+ NK cells from healthy volunteers. After the stimulation with immobilized anti-CD3 antibodies, both NK-type T cells produced much larger amounts of interferon-gamma (IFN-gamma) than CD8+ T cells. Both NK-type T cells also acquired a more potent cytotoxicity against NK-sensitive K562 cells than CD8+ T cells while only CD56+ T cells showed a potent cytotoxicity against NK-resistant Raji cells. After the stimulation with a combination of interleukin (IL)-2, IL-12 and IL-15, the IFN-gamma amounts produced were NK cells > or = CD56+ T cells > or = CD57+ T cells > CD8+ T cells. The cytotoxicities against K562 cells were NK cells > CD56+ T cells > or = CD57+ T cells > CD8+ T cells while cytotoxicities against Raji cells were CD56+ T cells > CD57+ T cells > or = CD8+ T cells > or = NK cells. However, the CD3-stimulated proliferation of both NK-type T cells was smaller than that of CD8+ T cells partly because NK-type T cells were susceptible to apoptosis. In addition to NK cells, NK-type T cells but not CD8+ T cells stimulated with cytokines, expressed cytoplasmic perforin and granzyme B. Furthermore, CD3-stimulated IFN-gamma production from peripheral blood mononuclear cells (PBMC) correlated with the proportions of CD57+ T cells in PBMC from donors. Our findings suggest that NK-type T cells play an important role in the T helper 1 responses and the immunological changes associated with ageing.

Adult↗

PubMed2001

Management of the axilla in breast cancer: a comparative study between sentinel lymph node biopsy and four-node sampling procedure.

BACKGROUND: The aim of this study was to compare the efficacy of sentinel lymph node biopsy and that of four-node sampling for predicting other nodal status in breast cancer. METHODS: 206 patients with operable breast cancer were enrolled. The identification of sentinel lymph nodes (SLNs) was carried out in 110 patients using a gamma probe after injection of radioactive tin colloids. Four palpable lymph nodes (FNs) were removed from the lower axilla at the first step of axillary dissection in 98 patients. The predictive value of nodal status was compared between SLNs and FNs, based on the pathological findings of all dissected lymph nodes. To examine the relationship between SLNs and FNs, we chose the FNs retrospectively (defined as rFNs) from among all nodes in SLNs. RESULTS: SLNs were identified in 108 (98%) of 110 patients. With one patient having skip metastasis, the accuracy and sensitivity were 99 and 98%, respectively. In the four-node sampling (FNS) group, two in 98 patients had skip metastasis and the accuracy and sensitivity were 98 and 96%, respectively. Findings on the relationship between these methods of biopsy were as follows: (i) rFNs included SLNs in 79 patients (73%); (ii) rFNs partially included SLNs in 24 patients (22%); and (iii) no relationship was evident in five patients (5%). CONCLUSIONS: The accuracy/sensitivity of FNs was comparable to that of SLNs. FNS can be considered to represent a highly promising approach and may be used as an alternative procedure that can be performed safely and easily in any institute.

Adult↗

PubMed2001

[Sentinel lymph node (SLN) in breast cancer: prediction of axillary metastasis confined to the SLN spares patients further axillary dissection].

Although regional control of the axilla in patients with breast cancer is important, axillary lymph node dissection (ALND) is performed mainly for staging purposes. The sentinel lymph node (SLN) that first receives lymphatic drainage from the tumor was investigated. After SLN identification, ALND or radiation therapy is performed in patients with SLN metastasis who are also likely to have non-SLN metastasis. However, it is important to select patients with SLN metastasis who may benefit from further axillary treatment. The size of the primary tumor and the size of its SLN metastasis are reported to be associated with the presence of non-SLN metastases. Patients in whom the SLN indicates less than 20% of nodes are involved have a low probability of non-SLN involvement and therefore can avoid further axillary treatment. Although large clinical trials are necessary for confirmation, it appear, that patients with axillary involvement confined to the SLN can be spread further ALND.

Axilla↗

PubMed2000

Mouse CD8+ CD122+ T cells with intermediate TCR increasing with age provide a source of early IFN-gamma production.

Although CD8+ IL-2Rbeta (CD122)+ T cells with intermediate TCR reportedly develop extrathymically, their functions still remain largely unknown. In the present study, we characterized the function of CD8+ CD122+ T cells with intermediate TCR of C57BL/6 mice. The proportion of CD8+ CD122+ T cells in splenocytes gradually increased with age, whereas CD8+ IL-2Rbeta-negative or -low (CD122-) T cells conversely decreased. The IFN-gamma production from splenocytes stimulated with immobilized anti-CD3 Ab in vitro increased with age, whereas the IL-4 production decreased. When sorted CD8+ CD122+ T cells were stimulated in vitro by the anti-CD3 Ab, they promptly produced a much larger amount of IFN-gamma than did CD8+ CD122- T cells or CD4+ T cells, whereas only CD4+ T cells produced IL-4. The depletion of CD8+ CD122+ T cells from whole splenocytes greatly decreased the CD3-stimulated IFN-gamma production and increased the IL-4 production, whereas the addition of sorted CD8+ CD122+ T cells to CD8+ CD122+ T cell-depleted splenocytes restored the IFN-gamma production and partially decreased IL-4 production. It is of interest that CD8+ CD122+ T cells stimulated CD4+ T cells to produce IFN-gamma. The CD3-stimulated IFN-gamma production from each T cell subset was augmented by macrophages. Furthermore, CD3-stimulated CD8+ CD122+ T cells produced an even greater amount of IFN-gamma than did liver NK1.1+ T cells and also showed antitumor cytotoxicity. These results show that CD8+ CD122+ T cells may thus be an important source of early IFN-gamma production and are suggested to be involved in the immunological changes with aging.

Aging↗

PubMed2000

Indications and technique of sentinel lymph node biopsy in breast cancer using 99m-technetium labeled tin colloids.

BACKGROUND: The status of the sentinel lymph node (SLN) can reflect the status of other lymph nodes in breast cancer. The efficacy of dye injection and radiolabeled tin colloids for the accurate identification of the SLN was investigated. The indications for SLN biopsy for determining clinical nodal status were also investigated. METHODS: A total of 108 patients with breast cancers less than 5 cm were enrolled. Ninety-six patients were clinically node negative and 12 were node positive. About 2 hours before surgery, 1 to 2.5 ml of 99m-technetium-labeled tin colloid was injected around the tumor. Just before the operation, dye was also injected into the tissue surrounding the tumor. Six clinically node negative patients were omitted from the dye-injection process. The SLN was identified as a lymph node with extremely high radioactivity using a gamma probe or a gamma counter. Complete axillary dissection was performed and the metastatic status investigated by hematoxylin and eosin staining. RESULTS: In clinically node negative patients undergoing dye-injection, the SLN was identified in 89 of 90 patients (98.9%), and there was only one patient with lymph node metastasis outside the SLN. However, in clinically node positive patients undergoing dye-injection, the identification rate of the SLN was 66.7% (8 of 12 patients) and there was one patient with lymph node metastasis outside the SLN (12.5%). Without dye-injection, the SLN could be detected in 4 of 6 patients (66.7%). CONCLUSIONS: Successful identification of the SLN with tin colloid requires concomitant dye-injection and candidates for SLN biopsy should be restricted to clinically node negative cases.

Adult↗

PubMed2000

Activation of monocytes and endothelial cells depends on the severity of surgical stress.

Surgical injury not only induces a systemic endocrine-metabolic response but also influences the function of the leukocytes and endothelial cells leading to various systemic responses. These responses appear to depend on the severity of surgical stress, which differs according to the surgical procedures. In this study, we investigated the response of monocytes and endothelial cells, and the development of systemic inflammatory response syndrome (SIRS) in relation to the severity of surgical stress. The postoperative clinical course was evaluated between patients undergoing an esophagectomy (ER group) and a distal gastrectomy (DG group). The tumor necrosis factor alpha (TNF-alpha) production of monocytes, the serum interleukin 6 (IL-6) levels, the CD11b expression on either monocytes or granulocytes, and the intercellular adhesion molecule-1 (ICAM-1) expression on human umbilical vein endothelial cells (HUVECs) stimulated with culture supernatants of monocytes were compared between the 2 groups. The development of SIRS was observed in all patients in the ER group, whereas no patients demonstrated SIRS in the DG group. The serum IL-6 levels, TNF-alpha production of monocytes, and CD11b intensity on monocytes or granulocytes in the ER group were higher than those in the DG group. In the ER group, the ICAM-1 intensity on HUVECs with monocytes immediately after operation significantly increased compared with before the operation. In conclusion, both the CD11b expression on monocytes and the TNF-alpha production of monocytes are considered to reflect the degree of surgical stress, and the activation of endothelial cells stimulated with these activated leukocytes may therefore lead to both tissue and organ injury.

Adenocarcinoma↗

PubMed2000

The liver as a crucial organ in the first line of host defense: the roles of Kupffer cells, natural killer (NK) cells and NK1.1 Ag+ T cells in T helper 1 immune responses.

The liver remains a hematopoietic organ after birth and can produce all leukocyte lineages from resident hematopoietic stem cells. Hepatocytes produce acute phase proteins and complement in bacterial infections. Liver Kupffer cells are activated by various bacterial stimuli, including bacterial lipopolysaccharide (LPS) and bacterial superantigens, and produce interleukin (IL)-12. IL-12 and other monokines (IL- 18 etc.) produced by Kupffer cells activate liver natural killer (NK) cells and NK1.1 Ag+ T cells to produce interferon-gamma and thereby acquire cytotoxicity against tumors and microbe-infected cells. These liver leukocytes and the T helper 1 immune responses induced by them thus play a crucial role in the first line of defense against bacterial infections and hematogenous tumor metastases. However, if this defense system is inadequately activated, shock associated with multiple organ failure takes place. Activated liver NK1.1 Ag+ T cells and NK cells also cause hepatocyte injury. NK1.1 Ag+ T cells and another T-cell subset with an intermediate T-cell receptor, CD 122+CD8+ T cells, can develop independently of thymic epithelial cells. Liver NK cells and NK1.1 Ag+ T cells physiologically develop in situ from their precursors, presumably due to bacterial antigens brought from the intestine via the portal vein. NK cells activated by bacterial superantigens or LPS are also probably involved in the vascular endothelial injury in Kawasaki disease.

Animals↗

PubMed2000

Primary small cell (oat cell) carcinoma of the breast: report of a case and review of the literature.

A case of primary small cell (oat cell) carcinoma of the breast in a 41-year-old woman is presented. The patient was alive and well without disease 16 months after modified radical mastectomy and subsequent chemotherapy. The tumor cells revealed morphologic similarity to oat cell carcinoma of the lung and immunohistochemical expression of neuroendocrine markers. In ultrastructural examination, the tumor cells had neurosecretory granules. Review of nine previously reported cases and this case of primary small cell carcinoma of the breast has revealed that this type of tumor shows prominent vascular invasion, frequent lymph node metastasis, infrequent expression of estrogen receptor, and also very poor prognosis. Immunohistochemical study for the c-kit proto-oncogene product, which has been reported to be a specific marker for pulmonary small cell carcinoma, demonstrated positive reactivity in approximately 80% of the tumor cells of this case, which is the first report according to our knowledge. The expression of c-kit might be some aid to the diagnosis of primary small cell carcinoma of the breast.

Adult↗

PubMed2000

Decrease of CD56(+)T cells and natural killer cells in cirrhotic livers with hepatitis C may be involved in their susceptibility to hepatocellular carcinoma.

CD56(+)T cells and CD56(+)natural killer (NK) cells are abundant in the human liver. The aim of this study was the further characterization of these cells in the liver with or without hepatitis C virus (HCV) infection. Liver mononuclear cells (MNC) were isolated from liver specimens obtained from the patients during abdominal surgery. In addition to a flow cytometric analysis, liver MNC and PBMC were cultured with the immobilized anti-CD3 Ab, IL-2, or a combination of IL-2 and IL-12 and their IFN-gamma production and the antitumor cytotoxicity were assessed. The liver MNC of HCV (-) patients contained 20% CD56(+)T cells whereas the same proportions decreased to 11% in chronic hepatitis livers and to 5% in cirrhotic livers. The proportion of NK cells also decreased in the cirrhotic livers. On the other hand, the populations of these cells in PBMC did not significantly differ among patient groups. The IFN-gamma production and the cytotoxicity against K562 cells, Raji cells, and a hepatocellular carcinoma, HuH-7 cells, greatly decreased in the cirrhotic liver MNC. In contrast, the cytotoxicity in PBMC did not significantly differ among the patient groups and was lower than that in the liver MNC of HCV (-) patients. CD56(+)T cells and NK cells but not regular T cells purified from liver MNC cultured with cytokines showed potent cytotoxicities against HuH-7 cells. These results suggest that a decreased number of CD56(+)T cells and NK cells in cirrhotic livers may be related to their susceptibility to hepatocellular carcinoma.

Aged↗

PubMed1999

Protective effect of NK1.1(+) T cells as well as NK cells against intraperitoneal tumors in mice.

Peritoneal resident cells of mice normally contain small populations of NK cells and NK1.1(+) alphabetaT cells. These populations increased after either 3LL or EL4 tumor inoculations into the peritoneal cavity. In vivo depletion of NK cell alone by anti-asialo GM1 (ASGM1) Ab significantly decreased survival time of tumor-injected mice, while depletion of both NK cells and NK1.1(+) T cells by anti-NK 1.1 Ab greatly shortened mouse survival time. NK1. 1(+) T cells in peritoneal cavity consist of a larger proportion of double-negative T cells and smaller populations of CD4(+) T cells and Vbeta8(+) T cells compared with liver NK1.1(+) T cells and normally lack Vbeta2(+) T cells. Tumor inoculation induced rapid IL-12 and IFN-gamma mRNA in tumor-infiltrating mononuclear cells (TIM). Although anti-NK1 Ab pretreatment in vivo abrogated IFN-gamma mRNA expression and IFN-gamma production of TIM, NK cell depletion alone by anti-ASGM1 Ab pretreatment retained IFN-gamma mRNA expression and partly inhibited IFN-gamma production of TIM. Peritoneal NK cells as well as NK1.1(+) T cells but not NK1.1(-) T cells of 3LL cell- or EL4 cell-injected mice showed cytotoxicities against the same tumor cells. Further, either anti-IL-12 Ab or anti-IFN-gamma Ab ip injection significantly shortened EL4 cell-inoculated mouse survival time. Our findings suggest that peritoneal macrophages activated by tumors produce IL-12 which activates NK cells and NK1.1(+) T cells to produce IFN-gamma and both NK cells and NK1.1(+) T cells are important in suppressing the growth of the intraperitoneal tumors.

Animals↗