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R Kiessling

Publications and source records attributed to R Kiessling.

At least 145 records · Page 8Linked to original sources
PubMed1980

A comparative analysis of the cell surface properties of activated vs endogenous mouse natural killer cells.

Mouse natural killer (NK) cells can be activated by interferon and by interferon inducers, such as viruses. In the present report we compared the cell surface properties of the nonactivated "endogenous" NK cells from normal mice with NK cells activated in vivo by acute infection with lymphocytic choriomeningitis virus (LCMV) or in vitro by interferon. Several striking differences were found: 1) in vivo LCMV-activated as well as in vitro interferon-activated NK cells were more adherent to nylon wool columns than the endogenous NK cells; 2) activated NK cells were more EA-monolayer adherent than endogenous NK cells; this adherence could be blocked by streptococcal A protein, indicating that activated NK cells expressed greater Fc receptor mediated adherence; 3) LCMV-activated NK cells that passed through nylon wool columns expressed relatively low EA adherence properties; 4) the sensitivity of NK cells to anti-theta serum + complement treatment was increased in spleen cells late after LCMV infection (day 6 to 7) but not in spleen cells early after infection (day 2 to 3); 5) as shown by centrifugal elutriation, LCMV-activated spleens contained a population of large NK cells that were not present among endogenous spleen cells. In contrast to previous reports, these findings show that there are several distinct changes as a result of both long-term in vivo activation or of short-term in vitro activation of NK cells. These changes might functionally be involved in the increased lytic ability of activated NK cells.

Animals↗
PubMed1980

Demonstration of natural antibodies in normal rabbit serum with similar specificity pattern as mouse natural killer cells.

Normal rabbit sera (NRS) obtained from noninbred animals were shown to contain antibody to YAC-1, a mouse lymphoma, in a complement-dependent 51Cr release assay. A positive correlation was found between the sensitivity to lysis by NRS antibody and the susceptibility to lysis by mouse natural killer (NK) cells when 7 mouse tumors and 1 guinea pig hepatoma were tested in both assay systems. This correlation was further established with a quantitative absorption assay in which NRS was absorbed with various mouse tumors and subsequently tested for cytotoxicity against YAC-1, the most NRS- and NK-sensitive tumor. A striking positive correlation appeared between the capacity to absorb the NRS anti-YAC-1 activity and the NK sensitivity of various mouse tumors to CBA spleen cells. Thymocytes from strain A/Sn mice less than 2 weeks old absorbed a substantial amount of the NRS anti-YAC-1 activity; these cells were also sensitive to mouse NK cytolysis, whereas thymocytes from older mice lacked both properties. These natural rabbit antibodies could not "arm" peripheral blood lymphocytes in the rabbit because 1) the peripheral blood lymphocytes from these animals used as serum donors showed only low cytotoxic activity in an NK assay against NK-sensitive mouse tumors, and 2) no positive correlation appeared between the levels of cytolytic activity and the levels of natural serum antibodies observed in the rabbits. The present data suggest that natural antibodies in NRS showed the same specificity pattern for mouse tumors displayed by mouse NK cells.

Age Factors↗
PubMed1980

Target-effector cell interaction in the natural killer cell system. V. Energy requirements, membrane integrity, and the possible involvement of lysosomal enzymes.

Various inhibitors were used to study further the mechanism of natural killing and to compare it to lympholysis by cytotoxic T lymphocytes (CTL). The respiratory inhibitors DNP and NaN3 or low temperatures (0 degrees) blocked the cell contact phase of target-effector interaction in the CTL system but not the NK system. The lytic stage was also inhibited by the glycolytic inhibitors, iodoacetate and NaF, in the NK system as previously shown in the CTL system. Dimethylsulphoxide, a dipolar solvent, and cytochalasin B, a microtubule disruptor, inhibited NK target binding. Pre-treatment of Nk cells with glutaraldehyde, a protein cross-linking agent, completely prevented lysis, but not the formation of target-effector conjugates. The lytic phase of NK lysis was inhibited by chloroquine which also inhibited lysosomal enzyme function. Lysosome defective, beige mutant mice were also totally deficient in NK lytic function and this defect could not be restored with cGMP. T-cell and macrophage mediated cytolysis was previously shown to be relatively normal in beige mice. These results suggest that (i) the mechanism of NK cytolysis is a complex, multistep process, and (ii) this process is fundamentally different from that occurring in CTL. A 'stimulus-secretion' model of NK cytolysis is presented in which it is postulated that lysosomal enzymes may be the lytic molecules.

Animals↗
PubMed1979

A functional comparison of tumor cell killing by activated macrophages and natural killer cells.

This report compares the sensitivity of 17 tumor cell lines to cytolysis mediated by natural killer (NK) cells or by activated, bone marrow-derived macrophages (AM) from 15 inbred mouse strains. Some tumor cell lines, notably P815, were highly sensitive to AM-mediated lysis but almost completely insensitive to NK cells, whereas other cell lines were lysed by NK cells but not AM. In a genotype survey, some low-responder strains in the NK system, such as A/Sn, were high responders in the AM system, and conversely, one intermediate to high-responder strain (C3H/HeJ) in the NK system was a low responder in AM-mediated cytolysis. In addition, macrophage cytotoxicity factor was necessary to activate macrophages, but this lymphokine did not augment NK activity. Furthermore, the NK population did not contain pre-activated macrophages since pre-activated cells were removed on glass bead columns or by iron carbonyl and a magnet; treatments which have been previously shown not to affect NK cells. These results suggest that NK cells are distinct from AM in physical characteristics, target selectivity, genotype distribution and the mechanism of cytolysis.

Animals↗
PubMed1979

Apparent identity of mechanisms of genetic resistance to marrow transplantation and natural killer cell activity.

Because the phenomenon of in vitro lysis of lymphoma cells by spleen natural killer (NK) cells bears genetic and effector cell resemblances to genetic resistance to bone marrow transplantation, they were compared for additional known unique characteristics of the latter phenomenon. Like GR to BMT, NK cell activity first appeared abruptly at about 3 weeks of post-natal age; was radioresistant to 1 100 R whole body irradiation, but was quantitatively diminished by higher exposures or delay of test post-irradiation; was suppressed by pretreatment with either cyclophosphamide, carrageenan, silica particles, anti-bone marrow serum or anti-thymus serum. The many unique identical characteristics of these two effector mechanisms indicates that they represent two manifestations of the same basic phenomenon of natural immunity. This is in accord with other data indicating that GR to BMT is directed at Hh antigens which, like TL antigens, may in some mouse strains appear on both leukemic cells and normal hemopoietic cells.

Animals↗
PubMed1978

Mouse natural killer (NK) cell activity against human cell lines is not influenced by superinfection of the target cell with xenotropic murine C-type virus.

Mouse natural killer (NK) cells can lyse a variety of syngeneic, allogeneic and xenogeneic target cells in short-term 51Cr release assays. The target specificity of NK cells is not known, but endogenous C-type viral antigens have been suggested as possible target structures. To test this hypothesis, human lymphoid lines were superinfected with xenotropic mouse C-type virus either by repeated dosage through nude mice or by in vitro superinfection with the supernatants of nude-mouse-passaged lines. The appearance of surface-associated MuLV antigens after superinfection was confirmed in a complement-dependent cytotoxicity test. Subsequently, the NK sensitivity of each infected line was compared with its non-infected counterpart in direct cytolytic and competition assays. None of these two assay systems showed a consistent difference in NK sensitivity of infected and non-infected cell lines. These findings do not lend support to the concept tht murine C-type viral antigens are responsible for NK sensitivity.

Animals↗
PubMed1978

Modulation of sensitivity to natural killer cell lysis after in vitro explantation of a mouse lymphoma.

On the basis of studies indicating that natural killer (NK) cells of the mouse can selectively kill certain syngenetic, allogeneic, and xenogeneic tumor cells in short-term Cr release assays and that cell lines established in vitro are more sensitive than the corresponding ascites tumor cells passaged in vivo, the kinetics of the modulation to increased sensitivity was studied after in vitro explanation of the A/Sn mouse-derived YAC ascites lymphoma. Sensitivity to NK lysis appeared after 3 weeks of culturing and reached the level of the continuously cultured line after 2 months. With the more sensitive competition assay, a change could be demonstrated as early as 2--24 hours of culture. The expression of the Moloney murine leukemia virus-determined, cell-surface antigen, measured by quantitative absorption with intact cells, increased in parallel with the NK sensitivity. In contrast, the H-2 alloantigen concentration decreased during in vitro culture.

Animals↗
PubMed1978

Intra- and interspecies reactivity of human and mouse natural killer (NK) cells.

Natural killer (NK) cells can kill certain syngeneic, allogeneic and xenogeneic tumor targets in short-term 51Cr release assays. In the present study, intra- and interspecies NK activity was analyzed. Ten mouse and five human tissue culture lines were used. In direct cytolytic assays with mouse spleen cells or human PBL effectors, intraspecies was much stronger than interspecies reactivity, as a rule. A certain interspecies activity was obtained, stronger in mouse anti-human (M alpha H) than in human anti-mouse (H alpha M) combinations. In the H alpha M system, activity was associated with the same type of PBL-derived non-B-non-T cell fraction as in the intraspecies H alpha H system. The non-B-non-T cell nature of the M alpha H killer cell has been demonstrated previously. Nonlabeled tumor cells were allowed to compete with isotope-labeled targets in intra- and interspecies cytolytic NK tests. NK-sensitive tumor lines of the same species were superior to xenogeneic competitors in both M alpha M and H alpha H tests. In the M alpha M assay, the competing ability of the same human tumors varied, depending on the genotype of the mouse effector cells. None of the human lines tested competed effectively with strain CBA effectors but some showed a certain competition with C57BL effectors. In the H alpha H assay, strong competition was seen with two of the 10 xenogeneic mouse tumors tested.

Animals↗