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T Hercend

Publications and source records attributed to T Hercend.

126 records · Page 7Linked to original sources

Phenotypic and functional heterogeneity of human cloned natural killer cell lines.

Extensive efforts have recently been made to characterize cells capable of mediating natural killing activity (see ref. 1 for review) and increasing evidence has arisen that these cells were heterogeneous. By using the methods we have recently developed for cloning natural killer (NK) cells derived from peripheral blood, we have analysed the heterogeneity of human NK cells. Seven cell lines showing NK activity were established and studied for 4 months. Their phenotype was determined with a series of monoclonal antibodies; anti-T1, -T3, -T4, -T8, -T11, -T12, Mo1 and each cell line appeared to have a unique phenotype. Moreover, whereas some of these lines could only kill K562 cells, the standard assay of NK activity, others displayed a broad but distinct spectrum of reactivity against a variety of human tumour and viral transformed cell lines. Taken together, these results demonstrate the phenotypic and functional heterogeneity of NK effector cells which has recently been suggested in both human and murine systems.

Cell Line↗

Characterization of an antigen expressed by human natural killer cells.

A monoclonal antibody, anti-N901, was produced by fusing NS-1 myeloma cells with spleen cells of a mouse immunized with human CML cells. This antibody was reactive with a subpopulation of peripheral blood LGL, including the natural killer cells. Monocytes, granulocytes, B cells, T cells (T3+ cells), erythrocytes, and platelets were nonreactive. The N901-positive cells in the peripheral blood were heterogeneous with respect to expression of other cell surface antigens. The majority of N901+ cells co-expressed T11, Mo1, and HNK-1, whereas a smaller percentage expressed T8. Ia, T3, T4, Mo2, or B1 antigens were very uncommon on N901+ cells. The heterogeneity of the N901+ LGL was further investigated by examining the expression of N901 antigen on a series of cloned normal human NK cell lines. N901 antigen was expressed by each of the NK cell lines tested, and by a minority of cloned T cell lines without NK activity. Anti-N901 does not block NK activity and can be used to rapidly purify functional NK cells for further study.

Animals↗

Surface structures involved in target recognition by human cytotoxic T lymphocytes.

Cloned human cytotoxic T lymphocytes and monoclonal antibodies inhibiting their function (anti-T3A, anti-T4A, and anti-T8A) were used to elucidate the role of T cell surface glycoproteins in cell-mediated lympholysis involving individual classes of gene products of the major histocompatibility complex on target cells. The results indicate that several surface molecules are required for specific target recognition: T3 and T4 on T4+ cytotoxic T lymphocytes and T3 and T8 on T8+ cytotoxic T lymphocytes.

Antibodies, Monoclonal↗

Autologous bone-marrow transplantation in CALLA-positive acute lymphoblastic leukemia after in-vitro treatment with J5 monoclonal antibody and complement.

A monoclonal antibody (J5) specific for the common acute-lymphoblastic-leukaemia antigen (CALLA) was used for in-vitro pre-treatment of bone-marrow before autologous transplantation in four patients with CALLA-positive acute lymphoblastic leukaemia (ALL) in relapse, who did not have HLA-compatible donors. After remission induction and intensification, bone-marrow cells were harvested, treated with J5 antibody and rabbit complement, and cryopreserved in liquid nitrogen. Patients received ablative chemotherapy and total-body irradiation before reinfusion of autologous J5-treated bone marrow. The transplantation protocol was well tolerated, and engraftment of normal myeloid cells occurred in all for patients. Two patients have continued in unmaintained remission with complete haematopoietic reconstitution for more than 1 year after autologous transplantation.

Antibodies, Monoclonal↗

[Stenosis of the right pulmonary artery secondary to carcinoma of the left lung. Effect of radiation therapy (author's transl)].

A case of undifferenciated carcinoma of the left lung with stenosis of the right pulmonary artery is reported. The characteristic clinical features of the systolic ejection murmur in pulmonary artery stenosis are recalled as well as the data from phonocardiographic, angiographic, and hemodynamic investigations. After radiation therapy, the grade of the systolic murmur decreased frankly although transiently. Noticeable decrease of the stenosis was substantiated by a second angiography. This improvement was still apparent 16 months later during chemotherapy.

Bronchial Neoplasms↗

Generation of a cloned NK cell line derived from the "null cell" fraction of human peripheral blood.

The present studies were designed to determine the conditions for generation of human NK clones. First the "null cell" (NC) fraction of human peripheral blood mononuclear cells, which contains the NK effectors, was purified using negative selection with anti-T3, anti-T8, anti-B1, and anti-Mo2 monoclonal antibodies. Subsequently, NC were cloned by limiting dilution using a combination of phytohemagglutinin (PHA) and lymphocyte-conditioned medium (LCM) as an initial stimulus. Colonies could be easily obtained with this procedure, but the maintenance of long-term growth of the cultures represented a major problem. A cloned cell line termed JT1 was generated and has been proliferating continuously in culture for more than 6 mo. The phenotype of JT1 cells was analyzed several times with a series of monoclonal antibodies. These cells did not express surface markers related to thymic (T3-, T4-, T8-, T11-), B cells (B1-, J5-), or myelomonocytic (Mo1-, Mo2-, MY7-) differentiation. In contrast, 95% of JT1 cells reacted with the anti-T10 monoclonal antibody. T9, Ia, and J2 antigens were also present on JT1 cells, but their expression appeared variable from one determination to another. This cloned cell line maintains a strong cytotoxicity against common NK targets, such as K562 and Molt 4 cell lines, and a moderate ADCC activity. In addition, after several months in culture, JT1 cells are still capable of being regulated by interferon, because this lymphokine rapidly enhances cytotoxicity against K562 cells.

Antibodies, Monoclonal↗

Correlation between precancerous bronchial metaplasia and cigarette consumption, and preliminary results of retinoid treatment.

Vitamin A and its derivatives, so-called retinoids, can prevent squamous metaplasia induced not only by vitamin A deficiency but also by carcinogenic hydrocarbons. An aromatic retinoid, such as ET1, has been shown to prevent chemically induced papillomas in mice and to amplify certain immunologic reactions. Heavy smokers, 106 volunteers, were submitted to fibrobronchoscopy with bronchial biopsies. An index of metaplasia (IM) was calculated on the basis of microscopical examination of a total of 9,633 sections of 1,010 biopsies. Despite the subjectivity of the estimates of cigarette consumption, this was significantly (P less than 0.02) and positively correlated to the IM. Eighty-five percent of the women had a low IM as compared to only 42% of the men (P less than 0.01), although there was no significant difference in the reported cigarette consumption. Fifty-two subjects had an IM greater than 15% and were given 25 mg ET1 orally daily for 6 months. The bronchoscopy was repeated in 30 patients following completion of the 6-month treatment. The IM was significantly (P less than 0.01) reduced after treatment.

Adult↗

Comparative expression of T9, T10, and Ia antigens on activated human T cell subsets.

In the present study, the expression of three surface molecules T9, T10, and Ia, which are found on activated T lymphocytes, was examined utilizing monoclonal antibodies and indirect immunofluorescence. These antigens were shown to appear on T lymphocytes in a defined temporal sequence which was dependent on the specific triggering stimulus. Moreover, when T cells were fractionated into individual subsets of T4+ inducer and T8+ cytotoxic/suppressor lymphocytes, the expression of all three molecules was restricted to the T4+ subset following soluble antigen stimulation. By contrast, both subsets expressed these surface determinants following mitogen or alloantigen stimulation. The above results suggest that there may be successive stages in the T cell activation process associated with the appearance of unique cell surface antigens and further support the view that various triggering stimuli activate T cell populations differently.

Antibodies, Monoclonal↗

Prevention of spontaneous tumors of aged mice by immunopharmacologic manipulation: study of immune antitumor mechanisms.

Effects produced by long-term application of three immune modifiers (azimexon, retinoic acid, and tuftsin) on the depressed immune systems of 18-month-old inbred C57BL/6 female mice were investigated. The effect of each agent was examined on four cell types (cytotoxic T-cells, K-cells, NK cells, and macrophages) possibly involved in antitumor defenses and on the spontaneous tumor development that accompanied advancing age. Three substances chosen for this study appeared able to alter immune parameters, and each one displayed its own pattern of activity. Common to all three agents were an increase of age-depressed tumoricidal activity of peritoneal macrophages and no effect on the depressed NK activity of spleen cells. Retinoic acid increased splenic K-cell activity, already elevated in aged mice and unaffected by the other two agents. Cytotoxic T-cell activity, diminished by age, was stimulated considerably by retinoic acid and by tuftsin but only slightly by azimexon. Histopathologic studies revealed a decrease in the incidence of spontaneous tumors in the 3 treated groups. This decrease was statistically significant in the retinoic acid- and tuftsin-treated groups when compared with the incidence in untreated mice of the same age. Correlation of drug-induced modifications of the immune system with tumor incidence in aged mice was attempted.

Adjuvants, Immunologic↗

T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV.

Many viruses, including retroviruses, are characterized by their specific cell tropism. Lymphadenopathy-associated virus (LAV) is a human lymphotropic retrovirus isolated from patients with acquired immune deficiency syndrome (AIDS) or related syndromes, that displays selective tropism for a subset of T lymphocytes defined by the expression of a surface glycoprotein of relative molecular mass 62,000 (62K) termed T4 (refs 6-8). This glycoprotein delineates a subset of T lymphocytes with mainly helper/inducer functions, while T lymphocytes of the reciprocal subset express a glycoprotein termed T8, have mainly cytotoxic/suppressor activities, and are unable to replicate LAV. Such a tropism may be controlled at the genomic level by regulatory sequences, as described for the human T-cell leukaemia viruses HTLV-I and -II (refs 2, 3). Alternatively or concomitantly, productive cell infection may be controlled at the membrane level, requiring the interaction of a specific cellular receptor with the virus envelope, as demonstrated recently for Epstein-Barr virus (EBV). Therefore, we have investigated whether the T4 molecule itself is related to the receptor for LAV. We report here that preincubation of T4+ lymphocytes with three individual monoclonal antibodies directed at the T4 glycoprotein blocked cell infection by LAV. This blocking effect was specific, as other monoclonal antibodies--such as antibody to histocompatibility locus antigen (HLA) class II or anti-T-cell natural killer (TNK) target--directed at other surface structures strongly expressed on activated cultured T4+ cells, did not prevent LAV infection. Direct virus neutralization by monoclonal antibodies was also ruled out. These results strongly support the view that a surface molecule directly involved in cellular functions acts as, or is related to, the receptor for a human retrovirus.

Antibodies, Monoclonal↗

A gamma-chain complex forms a functional receptor on cloned human lymphocytes with natural killer-like activity.

We have recently derived from human fetal blood (25 wks) a series of cloned cell lines that were selected for their ability to kill the conventional natural killer (NK) target cell K562. It was found that a fraction of these clones express CD3 proteins but not the monomorphic Ti alpha beta determinant recognized by WT31 antibody. One interleukin-2-dependent CD3+ WT31- clone, termed F6C7, was used for immunization of mice to generate monoclonal antibodies directed at a potentially novel recognition receptor. It was shown that F6C7 cells, which transcribe Ti beta but not Ti alpha genes, surface-express a clonotypic structure, termed NKFi. Immunoprecipitations performed with anti-NKFi monoclonal antibody (mAb) indicated that the corresponding molecule is resolved in SDS-polyacrylamide gel electrophoresis (PAGE) as a single band of relative molecular mass approximately 85,000 (Mr approximately 85K). After reduction, a major band was detected at 44K and a faint band was present at 41K. The present study was designed to characterize this structure. It was found that NKFi represents either two 44K disulphide-linked gamma (TCR) chains, or possibly one gamma chain associated to an additional undetected molecule, and that the 41K material corresponds to a partially glycosylated fraction of the gamma protein. Anti-NKFi mAb both induces a specific autocrine proliferative response and blocks cytotoxic function, demonstrating that gamma chains serve as functional receptor structures on subpopulations of normal human lymphocytes.

Antibodies, Monoclonal↗

[Two cases of tuberculosis of the skull cap (author's transl)].

The authors report two cases of tuberculosis of the skull cap. The first in a Black African with heterozygous sickle cell disease also presenting with: tuberculosis of the cervical lymph nodes, subcutaneous frontal tumefactions bacteriologically confirmed to be of tuberculous origin, multiple lacunae of the vault from the same origin; the second case is an Asian woman having a multifocal tuberculous osteitis involving the skull, spine, pelvis and probably the same affection in the spleen. These cases are a reminder that the principal features of tuberculosis of the skull vault are very often associated with other tuberculous lesions, and to the problems of diagnosis it entails; the existence of a subcutaneous tumefaction of the vault or of any accessible site one can aspirate and/or perform biopsy constitutes a diagnostic aid.

Adult↗