PubMed Health⌕ Search

Biomedical subjects

T Kalland

Publications and source records attributed to T Kalland.

At least 109 records · Page 6Linked to original sources
PubMed1987

Analysis of the murine lymphokine-activated killer (LAK) cell phenomenon: dissection of effectors and progenitors into NK- and T-like cells.

Murine as well as human lymphokine-activated killer (LAK) cells have been reported to have several characteristics of T lymphocytes and to be clearly distinct from natural killer (NK) cells. The present study of murine LAK cells showed that cytotoxic cells generated in the presence of interleukin 2 IL 2 were heterogeneous with respect to cell surface markers of progenitor as well as effector cells. Negative selection of cells with antibodies and complement or positive selection by fluorescence-activated cell sorting unequivocally showed that LAK effector cells consisted of at least two clearly distinct populations, the relative contribution of which was dependent on donor organ and target cells studied. Approximately 40% of the cytotoxic activity of spleen-derived effector cells active against the NK-resistant targets EL-4 or MCA-5 was eliminated by treatment with antibodies to the NK-markers asialo-GM1 and NK 1 (NK-LAK). Approximately 60% of cytotoxic activity was associated with cells expressing the T cell marker Lyt-2, lacked NK 1, and was lacking or expressed only small amounts asialo-GM1 (T-LAK). The NK-LAK cells were of greater importance for the cytotoxic activity against the standard NK target YAC-1, although T-LAK cells also excerted significant cytotoxicity against this cell line. Limiting dilution analysis estimated that the minimal frequency of precursors developing into cells with cytotoxic activity against EL-4 was 1/6700 in spleen and 1/4200 in peripheral blood. The frequency of cells developing into cytotoxic effectors against YAC-1 cells was 1/3700 and 1/1450 in spleen and peripheral blood, respectively. Depletion of progenitor cells from spleen or peripheral blood expressing NK 1 or Lyt-2 by treating the cells with antibodies to these structures and complement indicated that NK-1-expressing cells were the dominating progenitor of the LAK cells irrespective of target cells used. Culture of murine lymphoid cells from spleen or peripheral blood with high concentrations of IL 2 results in the emergence of two different killer cell populations with phenotypic similarities to NK and T cells, respectively, both being able to kill targets resistant to resting NK cells. In contrast to numerous earlier reports, we concluded that LAK cells are heterogeneous with respect to surface markers, with a major population of LAK cells apparently representing IL 2-activated cells expressing cell surface markers associated with NK cells.

Animals↗
PubMed1987

Functionally involved cell surface antigens on murine lymphokine activated killer cells.

To investigate the possible involvement of some cell surface structures on lymphoid cells in the functional activity of lymphokine activated killer (LAK) cells, a number of monoclonal antibodies (Mab) against such structures was studied for their ability to inhibit LAK activity in a standard cytotoxicity assay against the natural killer-insensitive target cell EL-4. Almost complete inhibition of LAK activity resulted from incubation with antibodies to the LFA-1 antigen, while blocking of the Lyt 2 antigen reduced cytotoxic activity about 50%. Mab to T-200 gave a weak and inconsistent inhibitory activity, while antibodies to Thy 1, L3T4, IL-2 receptor and MHC class I antigens were without effect. Mab to LFA-1 and Lyt 2 inhibited LAK activity towards EL-4, YAC-1 and differentiated F-9 teratocarcinoma cells, but did not affect LAK-mediated killing of undifferentiated F-9 cells. Experiments with separate preincubation of effector and target cells revealed that both LFA-1 and Lyt 2 inhibited LAK activity at the effector cell level only.

Animals↗
PubMed1986

Interleukin 3 is a major negative regulator of the generation of natural killer cells from bone marrow precursors.

We have established a bone marrow culture system in which mature natural killer (NK) cells can be generated from inactive precursors by interleukin 2. Recombinant interleukin 3 (IL 3) almost completely blocked the induction of NK cells in this culture system as judged by cytotoxic activity, as well as appearance of cells with NK phenotype. The dose-response curve for inhibition of the generation of NK activity with IL 3 parallelled the growth promoting activity on the strictly IL 3-dependent cell line L/B. The effect of IL 3 was selective for the precursor stage of the NK cell, because mature NK cells were not affected by culture with IL 3 for the same period of time. Moreover, the effect of IL 3 was confined to the first 24 hr of culture, indicating an effect on an early stage of NK cell differentiation. IL 3 did not increase the small normally occurring NK-sensitive population in bone marrow, and did not affect the activity of a variant cytotoxic cell with specificity for adherent target cells, the natural cytotoxic cell. Concomitantly with downregulation of NK cell generation, IL 3 induced strong proliferation in the bone marrow cultures and an increase in the percentage of cells expressing the T cell marker Thy-1. A model for regulation of NK cells based on competition of growth factors for target cells with a common progenitor is discussed.

Animals↗
PubMed1986

Effects of the novel immunomodulator LS 2616 on the delayed-type hypersensitivity reaction to Bordetella pertussis in the rat.

Treatment of Sprague-Dawley rats with the compound LS 2616, a quinoline-3-carboxamide, enhanced the delayed-type hypersensitivity response (DTH) to recall antigens as judged by the specific accumulation of inflammatory cells after challenge with Bordetella pertussis in the pleural space. LS 2616 was effective when given both before sensitization and at the time of secondary antigen challenge. The effect of LS 2616 on DTH was dose-dependent. LS 2616 was highly effective in enhancing DTH in rats with suppressed cell-mediated immunity after treatment with anti-thymocyte globulin or prednisolone, indicating its possible value in the immunosuppressed state.

Adjuvants, Immunologic↗
PubMed1986

Generation of natural killer cells from bone marrow precursors in vitro.

A simple and highly reproducible bone marrow culture system for the generation of cytolytically active NK cells from immature precursors in the bone marrow is described. The NK cells can be generated with various sources of IL-2, including Con A-conditioned medium, supernatants from IL-2-producing cell lines and recombinant IL-2. Neither IL-1, IL-3 nor alpha/beta interferon induced significant cytotoxicity in bone marrow cells. Identification of the cytotoxic cells as NK cells was based on their phenotypic characteristics (aGM1+, Thy 1 +/-, Ly 1-2- X Ia-, RIL-2 +/-, H2+), as well as their spectrum of target specificity. The deliberate addition of peripheral blood mononuclear cells as a source of mature NK cells and elimination of cells expressing markers specific for mature NK cells indicated that the generated NK cells were descendants of precursors of NK cells harboured in the bone marrow and not derived from mature NK cells contaminating the bone marrow preparations. Thus, it was shown that not only functionally active NK cells but also their precursors are highly dependent on IL-2 for differentiation and growth. This culture system should be helpful in studying the origin of NK cells in relation to other cell lineages as well as the regulation of the maturation of NK cells from their precursors.

Animals↗
PubMed1986

Effects of the immunomodulator LS 2616 on growth and metastasis of the murine B16-F10 melanoma.

The carboxamide-quinoline LS 2616 is a novel immunomodulator augmenting natural killer (NK) cell activity and T-lymphocyte related effector functions. To investigate the possible usefulness of LS 2616 in immunotherapy of tumors, the effect of the substance on growth and metastasis of the B16-F10 melanoma in syngeneic C57BL/6 mice was investigated. Treatment with LS 2616 from the time of s.c. inoculation of B16-F10 cells significantly reduced tumor take. Continuous treatment of mice with LS 2616 initiated 4 days prior to i.v. injection of tumor cells reduced the number of pulmonary metastases by 85%. When treatment with LS 2616 was started 4 days after i.v. injection of tumor cells, a time when established tumor foci were readily detectable in the lungs, a significant reduction in the number of pulmonary metastases resulted. LS 2616 significantly reduced the number of spontaneous pulmonary metastases developing from a B16-F10 tumor growing in the footpad. When treatment with LS 2616 was initiated after the establishment of grossly visible spontaneous pulmonary metastases, no significant effect on the number of metastases was found after 2 weeks of treatment. However, combined treatment with a dose of cyclophosphamide which in itself was ineffective resulted in a statistically significant 70% reduction in the number of remaining pulmonary metastases. Injection of antibodies to asialomonoganglioside which strongly reduce NK cell activity in various organs was used as a probe for the involvement of NK cells in the effects of LS 2616 on the B16-F10 tumor. The therapeutic efficiency of LS 2616 on tumor take when given from the time of s.c. inoculation, on the number of i.v. induced pulmonary metastases when treatment was started before tumor cell injection, as well as the spontaneous development of pulmonary metastases during exposure to the substance was abrogated by simultaneous injection with antibodies to asialomonoganglioside. In contrast, the beneficial effects of LS 2616 on already established i.v. produced or spontaneous pulmonary metastases were unaltered in mice made NK cell deficient by injection of anti-asialomonoganglioside antibodies. In conclusion, LS 2616 has potent antitumor activities mediated by NK cells as well as non-NK cell related defense mechanisms.

Adjuvants, Immunologic↗
PubMed1985

Inhibition of T lymphocyte activation by estramustine: dose-dependent interference with IL-2 production and later proliferation events.

Estramustine, a nitrogen mustard derivative of estradiol-17 beta widely used for treatment of prostatic cancer, was found to inhibit the proliferative response of mouse lymphocytes to T (concanavalin A) and B (lipopolysaccharide) cell mitogens in vitro. Concanavalin A-induced lymphoproliferation was considerably more sensitive to the antiproliferative effect of estramustine than lipopolysaccharide-stimulated proliferation. The concentration of estramustine selectively inhibiting T lymphocyte proliferation was only active when present during the first 24 h of culture and could be overcome by exogenously added interleukin 2. Estramustine was shown to directly inhibit the production of interleukin 2 in concanavalin A-stimulated lymphocyte cultures without affecting the expression of interleukin 2 receptors. Thus the preferential inhibitory effect of estramustine on mitogen-induced T lymphocyte activation is apparently mediated by interference with the production or release of interleukin 2.

Animals↗
PubMed1985

A study of some immunological variables in twins, discordant for multiple sclerosis.

11 twin pairs, discordant for multiple sclerosis (MS), were studied: 5 were monozygotic, 6 dizygotic. The mixed leukocyte reaction (MLR) with cells from unrelated patients with MS, the natural killer cell (NK) activity, OKT 4/OKT 8 ratio, and monocyte numbers were studied. The impaired MLR seen in some patients with MS was even more pronounced in the healthy twin, irrespective of the zygosity of the twins. A reduced NK activity and a high OKT 4/OKT 8 ratio is seen in the diseased twin compared to the healthy one, more strongly indicated at monozygosity. The significance of genetics, early environment, and disease is discussed.

Adult↗
PubMed1985

Augmentation of mouse natural killer cell activity by LS 2616, a new immunomodulator.

The quinoline-3-carboxamide LS 2616 administered to mice in drinking water increased spontaneous cytotoxicity against YAC-1 cells in a dose-dependent manner. The enhancement of spontaneous cytotoxicity was found to be mediated by NK cells, as judged by their lack of adherence to nylon wool columns, relative resistance to treatment with antibodies to Thy-1.2 and complement, and almost total abrogation after depletion of asialo-GM1+ cells. Enhancement of NK activity was evident after 2 days of treatment, was maximal after 4 days, and remained elevated during the 14-day exposure period studied. NK activity returned to control levels 4 days after cessation of treatment. NK activity was significantly increased in spleen, peripheral blood, lymph nodes, and bone marrow of LS 2616-treated mice, while activity in peritoneal exudate cells and thymus remained low. LS 2616 was able to elevate NK activity in several mouse strains studied, including mice homozygous for the beige gene. Serum interferon levels were not increased during treatment with LS 2616. Combined injection of the interferon inducer Poly I:C and LS 2616 did not increase NK activity above that of animals injected with Poly I:C alone. However, Poly I:C, in contrast to LS 2616, increased NK activity in peritoneal exudate cells. Studies at the single cell level revealed that LS 2616 increased NK activity by increasing the number of lytically active cells via recruitment of new target-binding cells and not by increasing the lytic activity of pre-existing binders.

Adjuvants, Immunologic↗
PubMed1984

Effects of diethylstilbestrol and estramustine phosphate (estracyt) on natural killer cell activity and tumor susceptibility in male mice.

The effects of estramustine phosphate (EMP) and diethylstilbestrol (DES) on natural killer (NK) cell activity, tumor growth, and artificial metastases were investigated in male C57BL/6 mice. Kinetic analysis and studies at the single-cell level indicated that EMP did not influence the number of NK cells but interfered with their lytic activity thereby reducing the actual killer capacity. NK cells from EMP-exposed animals responded normally to the interferon inducer Poly I:C which restored NK activity to control levels. Spleen cells from DES-treated animals had lytic activity comparable to that of control animals. However, more detailed analysis showed that DES reduced the number of lymphocytes able to recognize target cells, while the individual NK cell had an increased lytic activity and recycling capacity. Moreover, NK cells from DES-treated animals were refractory to poly-I:C stimulation, suggesting that they were prestimulated in vivo. The pertubations of the NK cell system induced by both EMP and DES were reversible and normalization of NK activity was reached within a week. The incidence of tumor takes after subcutaneous inoculation of the syngeneic Lewis lung carcinoma was increased in EMP as well as DES-treated animals. Artificial lung metastasis produced by intravenous injection of the same tumor was increased in EMP but not in DES-exposed animals.

Animals↗
PubMed1984

Effects of diethylstilbestrol on human natural killer cells in vitro.

Exposure of human peripheral blood lymphocytes to diethylstilbestrol (DES) in vitro resulted in inhibition of Natural Killer (NK) cell activity. DES inhibited NK activity in a dose and time-dependent manner with maximal effect after an 18 h exposure time. Significant reduction in cytotoxicity was obtained at concentrations of DES equal to or above 1 microM. The DES-induced inhibition of NK activity was reversible and totally abrogated within 18 h of culture in the absence of DES. Studies at the single cell level revealed that DES impaired the lytic activity of NK cells without interfering with recognition of target cells. The presence of indomethacin or aspirin during exposure to DES completely reversed the DES-induced inhibition of NK activity, indicating that a product of the cyclooxygenase system mediated the suppression.

Cell Line↗
PubMed1984

Exposure of neonatal female mice to diethylstilbestrol persistently impairs NK activity through reduction of effector cells at the bone marrow level.

Female NMRI mice neonatally treated with diethylstilbestrol (DES) show persistent impairment of various immune parameters, including NK activity. The present study demonstrated that NK activity was reduced in all lymphoid compartments and thus is not due to a simple redistribution of effector cells. Poly I:C was unable to augment NK activity in DES treated animals in vitro and in vivo. This defect was not attributable to inability to produce interferon in response to poly I:C since interferon-beta was also unsuccessful in augmenting NK activity in vitro. Moreover, the lack of response was not dependent on alterations in macrophage function, as evident from experiments showing that macrophages from DES-exposed animals resulted in a normal enhancement of NK activity in response to poly I:C when mixed with lymphocytes from control animals. Studies at the single cell level revealed that the reduced NK activity was the result of a reduced number of target-binding effector cells, and that the individual cells actually binding a target killed the target in an apparently normal fashion. Adoptive transfer of bone marrow cells between control and neonatally DES-treated animals showed that the reduced number of effector cells was determined at the bone marrow level.

Animals↗
PubMed1984

The effect of 3-methylcholanthrene on mouse natural killer cells in vitro.

The effect of the chemical carcinogen 3-methylcholanthrene (3-MCA) on mouse natural killer (NK) cells was tested in vitro applying kinetic analysis of the NK-tumor cell interaction. 3-MCA inhibited the lytic activity of spleen cells against YAC-1 target cells in a dose-dependent manner. Maximal inhibition, of Vmax was about 60% and a parallell decrease in KM values was observed. Inhibition was observed after 30 min preincubation of effector cells while pre-incubation of target cells had no effect. Inclusion of Indomethacin in the assay to exclude the possibility that prostaglandins induced by 3-MCA were the mediators of NK suppression had no effect. 3-MCA inhibited basal and interferon-activated NK lysis to about the same extent, while Vmax and KM values of effector cells pretreated with 3-MCA and assayed in the presence of interferon was close to control values. In a single cell assay for NK activity it was found that 3-MCA interfered with the lytic step of NK mediated lysis without affecting target binding. These data are in accordance with an earlier observation that a single injection of 3-MCA transiently inhibited mouse NK cells in vivo and evidence is presented that 3-MCA inhibits the lytic activity of a subpopulation of NK cells. The effects of 3-MCA were reversed by interferon.

Animals↗
PubMed1984

Enhancement of mouse natural killer cell activity after dearterialization of experimental renal tumors.

Dearterialization of intrarenally transplanted syngeneic or allogeneic tumors in C57Bl/6 mice resulted in a pronounced enhancement of spontaneous cell mediated cytotoxicity of spleen lymphocytes. The augmentation was evident 48 hours after occlusion of the renal artery and persisted for at least 1 week. Dearterialization of non-tumor bearing kidneys had no effect on spontaneous cell mediated cytotoxicity. The effector cells responsible for the increased cytotoxicity were identified as natural killer cells based on their lack of adherence to nylon-wool, resistance to treatment with Thy 1.2 antibodies and complement and complete elimination by antibodies to asialo-GM1 and complement. The increase in natural killer cell activity reported here is in close parallel to that observed after embolization of human renal tumors. The present murine system may provide a valuable tool for evaluation of immunobiological effects of tumor dearterialization.

Animals↗
PubMed1984

Back-crossing F1 (BN X PVG) rats with the PVG strain gives hybrids with high natural killer (NK) cell activity.

The genetic regulation of rat natural killer (NK) cell activity against the lymphoma YAC-1 in two rat strains, BN and PVG, with low and intermediate NK activity respectively, was studied. The F1 (BN X PVG) and the BN X F1 (BN X PVG) hybrids were both found to have NK activity intermediate between the BN and PVG parental strains, whereas approximately half of the PVG X F1 (BN X PVG) had high NK activity. No correlation to AgB types was found. Apparently at least two genes regulate NK activity in the rat, neither of which appears to be linked to the major histocompatibility complex.

Animals↗
PubMed1984

Characterization of effector cells mediating the augmentation of spontaneous cell-mediated cytotoxicity induced by therapeutic infarction of human renal carcinomas.

Spontaneous cell-mediated cytotoxicity has been shown to be augmented after therapeutic infarction of human renal carcinomas. The effector cell responsible for the enhanced cytotoxicity was characterized by fractionation by adherence to nylon-wool and serum-coated plastic surfaces, density, and reactivity with certain monoclonal antibodies. The effector cell was nonadherent, sedimented in the lighter fractions of a 40-53% discontinuous Percoll gradient, and was not affected by preincubation with OKT 3 antibody selectively blocking cytotoxic T lymphocytes. About 70% of effector cells expressed the HNK-1 and 50% the OKM-1 antigenic markers. Cytotoxicity was high against the NK-sensitive target K-562 and low against the relatively NK-resistant target cell Daudi. These data define the effector cell mediating the increased cell-mediated cytotoxicity induced by infarction of renal carcinomas as a natural killer cell.

Carcinoma, Renal Cell↗
PubMed1984

Occlusion of renal arterial tumor supply with absolute ethanol. Experience with 20 cases.

Absolute ethanol was used for renal ablation in 20 patients with carcinoma of the kidney. The procedure was followed by nephrectomy in 6 patients without metastases, all of whom are alive without evidence of recurrence 4 to 20 months after treatment. Fourteen patients with metastatic or locally advanced disease were embolized to palliate pain or hematuria without subsequent nephrectomy. Of these only 2 are alive, 4 and 18 months following the procedure. The technique for ethanol embolization is described and the use of occluding balloon catheters is recommended. No complications were encountered and the 'postembolization syndrome' was less marked as compared with a previous material of equal size where other methods of renal artery occlusion were employed. Microscopic examination in 10 of the infarcted kidneys showed extensive tumor necroses, sometimes with no evidence of viable tumor cells at all. Natural killer cell activity was determined before and 48 hours after renal artery occlusion in 7 patients, showing somewhat increased activity in 4. It is concluded that absolute ethanol is a safe, effective and easily administered agent for the infarction of renal tumors.

Adenocarcinoma↗