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A list of articles related to immunology research are presented. They include "Dose dependent modulation of CD8 and functional avidity as a result of peptide encounter," "Expression of 5-lipoxygenase (5-LOX) in T lymphocytes," and "Salmonella-induced SipB-independent cell death requires TLR4 signalling via the adapter proteins Tram and Trif."

Heat-shock proteins (hsp) represent a highly conserved family of proteins, normally localized in the cytoplasm and nucleus, whose expression is induced in situations involving cell stress. This paper reports the unusual translocation of hsp to the cell membrane of T cells undergoing apoptosis. We observed that glucocorticosteroid-induced thymocyte death is associated to the surface expression of hsp 60 and hsp 70 in a discrete fraction of apoptotic cells, hsp surface expression is closely related to a thymic subset of immature CD3low/- T cells. The expression of surface hsp 60 appears early after treatment with dexamethasone (3 hr) whereas the membrane expression of hsp 70 follows different kinetics and peaks later. Morphological analysis of the hsp+ apoptotic cells suggest that this subset represents late-stage apoptotic cells at their minimal volume before fragmentation into apoptotic bodies, Membrane expression of hsp is also associated with apoptosis in peripheral blood mononuclear cells from AIDS patients cultured in vitro. Altogether, we show that a discrete fraction of cells undergoing apoptosis expresses membrane hsp 60 and hsp 70, supporting the hypothesis that apoptosis causes a radical alteration in the expression of cell surface molecules. Surface hsp expressed during apoptosis may constitute a novel immune-context able to generate packages of self- and exogenous antigens, originating from degradation of altered cells. [ABSTRACT FROM AUTHOR]

Lymph node and spleen cells from normal mice were cultured for 3 days with polyoma virus-induced tumour, Ehrlich's ascites turnout or leukaemia L 1210 cells. This resulted in in vitro immunization of the lymphocytes, which were then transferred to irradiated target cells labelled with 51Cr. Normal, i.e. non-immune thioglycollate-stimulated peritoneal macrophages were also added to some tubes. Non-immune macrophages mixed with immunized lymphocytes showed a significantly increased ability to destroy tumour ceils as compared with macrophages in the absence of immunized lymphocytes. The immunized lymphocytes were almost entirely inactive alone. When the number of macrophages was kept constant the cytotoxicity was dependent on the number of viable immunized lymphocytes placed on the target cells. Immunized lymphocytes, in the presence of macrophages, only exhibited strong killing of the target cells against which they had been immunized; some lysis of ‘bystander’ cells was, however, seen provided specific target cells were present. Macrophage monolayers exposed to immunized lymphocytes upon contact with specific antigen became ‘armed’ and showed a significant cytotoxicity for specific target cells. When immunized lymphocytes and normal macrophages were treated with actinomycin D and puromycin, cytotoxicity was inhibited in the immunized lymphocytes but not in the macrophages. The possible mechanism of normal macrophage cooperation with immunized lymphocytes in the cytotoxic killing reaction is discussed. Results presented in this paper favour the view that immunologically specific cytophilic factor (presumptive cytophilic antibody) is involved in the macrophage-mediated cytotoxicity in the system studied. [ABSTRACT FROM AUTHOR]

Published data for the Streptococcus pneumoniae virulence factor Pneumolysin (Ply) show contradictory effects on the host inflammatory response to infection. Ply has been shown to activate the inflammasome, but also can bind to MRC‐1 resulting in suppression of dendritic cell inflammatory responses. We have used an in vitro infection model of human monocyte‐derived macrophages (MDM), and a mouse model of pneumonia to clarify whether pro‐ or anti‐inflammatory effects dominate the effects of Ply on the initial macrophage inflammatory response to S. pneumoniae, and the consequences during early lung infection. We found that infection with S. pneumoniae expressing Ply suppressed tumour necrosis factor (TNF) and interleukin‐6 production by MDMs compared to cells infected with ply‐deficient S. pneumoniae. This effect was independent of bacterial effects on cell death. Transcriptional analysis demonstrated S. pneumoniae expressing Ply caused a qualitatively similar but quantitatively lower MDM transcriptional response to S. pneumoniae compared to ply‐deficient S. pneumoniae, with reduced expression of TNF and type I IFN inducible genes. Reduction of the MDM inflammatory response was prevented by inhibition of SOCS1. In the early lung infection mouse model, the TNF response to ply‐deficient S. pneumoniae was enhanced and bacterial clearance increased compared to infection with wild‐type S. pneumoniae. Overall, these data show Ply inhibits the initial macrophage inflammatory response to S. pneumoniae, probably mediated through SOCS1, and this was associated with improved immune evasion during early lung infection. [ABSTRACT FROM AUTHOR]

Regulated or programmed cell death plays a critical role in the development and tissue organization and function. In addition, it is intrinsically connected with immunity and host defence. An increasing cellular and molecular findings cause a change in the concept of cell death, revealing an expanding network of regulated cell death modalities and their biochemical programmes. Likewise, recent evidences demonstrate the interconnection between cell death pathways and how they are involved in different immune mechanisms. This work provides an overview of the main cell death programmes and their implication in innate immunity not only as an immunogenic/inflammatory process, but also as an active defence strategy during immune response and at the same time as a regulatory mechanism. [ABSTRACT FROM AUTHOR]

Summary: Interleukin‐1β (IL‐1β) plays pivotal roles in controlling bacterial infections and is produced after the processing of pro‐IL‐1β by caspase‐1, which is activated by the inflammasome. In addition, caspase‐1 cleaves the cytosolic protein, gasdermin‐D (GSDMD), whose N‐terminal fragment subsequently forms a pore in the plasma membrane, leading to the pyroptic cell‐death‐mediated release of IL‐1β. Living cells can also release IL‐1β via GSDMD pores or other unconventional secretory pathways. However, the precise mechanisms are poorly defined. Here, we show that lipoproteins from Mycoplasma salivarium (MsLP) and Mycoplasma pneumoniae (MpLP) and an M. salivarium‐derived lipopeptide (FSL‐1), which are activators of the nucleotide‐binding oligomerization domain‐like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, induce IL‐1β release from mouse bone‐marrow‐derived macrophages (BMMs) without inducing cell death. The levels of IL‐1β release induced by MsLP, MpLP and FSL‐1 were more than 100 times lower than those induced by the canonical NLRP3 activator nigericin. The IL‐1β release‐inducing activities of MsLP, MpLP and FSL‐1 were not attenuated in BMMs from GSDMD‐deficient mice. Furthermore, both active caspase‐1 and cleaved GSDMD were detected in response to transfection of FSL‐1 into the cytosol of BMMs, but the release of IL‐1β was unaffected by GSDMD deficiency. Meanwhile, punicalagin, a membrane‐stabilizing agent, drastically down‐regulated the release of IL‐1β in response to FSL‐1. These results suggest that mycoplasmal lipoprotein/lipopeptide‐induced IL‐1β release by living macrophages is not mediated via GSDMD but rather through changes in membrane permeability. [ABSTRACT FROM AUTHOR]

Summary: Microglial inflammation driven by the NACHT, LRR and PYD domain‐containing protein 3 (NLRP3) inflammasome contributes to brain disease and is a therapeutic target. Most mechanistic studies on NLRP3 activation use two‐dimensional pure microglial cell culture systems. Here we studied the activation of the NLRP3 inflammasome in organotypic hippocampal slices, which allowed us to investigate microglial NLRP3 activation in a three‐dimensional, complex tissue architecture. Toll‐like receptor 2 and 4 activation primed microglial inflammasome responses in hippocampal slices by increasing NLRP3 and interleukin‐1β expression. Nigericin‐induced NLRP3 inflammasome activation was dynamically visualized in microglia through ASC speck formation. Downstream caspase‐1 activation, gasdermin D cleavage, pyroptotic cell death and interleukin‐1β release were also detected, and these findings were consistent when using different NLRP3 stimuli such as ATP and imiquimod. NLRP3 inflammasome pathway inhibitors were effective in organotypic hippocampal slices. Hence, we have highlighted organotypic hippocampal slice culture as a valuable ex vivo tool to allow the future study of NLRP3 inflammasomes in a representative tissue section, aiding the discovery of further mechanistic insights and drug development. [ABSTRACT FROM AUTHOR]

Acquisition of a 'quiescence programme' by naive T cells is important to provide a stress-free environment and resistance to apoptosis while preserving their responsiveness to activating stimuli. Therefore, the survival and proper function of naive T cells depends on their ability to maintain quiescence. Recently we demonstrated that by preventing chronic unresolved endoplasmic reticulum ( ER) stress, Schlafen2 (Slfn2) maintains a stress-free environment to conserve a pool of naive T cells ready to respond to a microbial invasion. These findings strongly suggest an intimate association between quiescence and stress signalling. However, the connection between ER stress conditions and loss of T-cell quiescence is unknown. Here we demonstrate that homeostasis of cholesterol and lipids, is disrupted in T cells and monocytes from Slfn2-mutant, elektra, mice with higher levels of lipid rafts and lipid droplets found in these cells. Moreover, elektra T cells had elevated levels of free cholesterol and cholesteryl ester due to increased de novo synthesis and higher levels of the enzyme HMG-CoA reductase. As cholesterol plays an important role in the transition of T cells from resting to active state, and ER regulates cholesterol and lipid synthesis, we suggest that regulation of cholesterol levels through the prevention of ER stress is an essential component of the mechanism by which Slfn2 regulates quiescence. [ABSTRACT FROM AUTHOR]

Cell stress of various kinds can lead to the induction of cell death and a damaging inflammatory response. Hence, a goal of therapeutic cell-stress management is to develop agents that might effectively regulate undesirable cell death and inflammation. To that end, we developed a synthetic peptide of seven amino acids based on structural mimicry to a functional domain of p53, a key factor in the responses of cells to stressful stimuli. This heptapeptide, which we term Stressin-1, was found to inhibit both cell death and the secretion of inflammatory mediators by various cell types in response to different stressful agents in vitro. The combined anti-inflammatory and anti-apoptotic activities of Stressin-1 were associated with a cellular signalling cascade that induced activation of Akt kinase and activation of the cAMP response element-binding protein (CREB) transcription factor. These immediate signalling events led to the inhibition of the signal transducer and activator of transcription and nuclear factor- κB pathways 24 hr later. Unexpectedly, we found no evidence for a direct involvement of p53 in the effects produced by Stressin-1. Intraperitoneal administration of 100 μg of Stressin-1 to lethally irradiated mice significantly protected them from death. These findings show that activating the Akt- CREB axis with Stressin-1 can counteract some of the undesirable effects of various cell stresses. Stressin-1 may have clinical usefulness. [ABSTRACT FROM AUTHOR]

Salmonella enterica serovar typhimurium ( S. typhimurium) is an intracellular pathogen that causes macrophage cell death by at least two different mechanisms. Rapid cell death is dependent on the Salmonella pathogenicity island-1 protein SipB whereas delayed cell death is independent of SipB and occurs 18–24 hr post infection. Lipopolysaccharide (LPS) is essential for the delayed cell death. LPS is the main structural component of the outer membrane of Gram-negative bacteria and is recognized by Toll-like receptor 4, signalling via the adapter proteins Mal, MyD88, Tram and Trif. Here we show that S. typhimurium induces SipB-independent cell death through Toll-like receptor 4 signalling via the adapter proteins Tram and Trif. In contrast to wild type bone marrow derived macrophages (BMDM), Tram–/– and Trif–/– BMDM proliferate in response to Salmonella infection. [ABSTRACT FROM AUTHOR]

Recently, we have described a soluble survival signal for activated lymphocytes from CD14+ cells. As a result of the importance of T lymphocytes in the pathogenesis of rheumatoid arthritis (RA), we speculate a possible role for CD14+ cells in supporting the outgrowth of autoreactive lymphocytes in RA. To address this issue further, supernatants from activated CD14+ cells (CD14 cocktails) in both normal controls and RA patients were collected. The relative strength of the CD14 cocktails from normal controls and RA patients was compared. The data showed that depletion of CD14+ calls resulted in a much higher increase of activation-induced cell death (AICD) and a decrease of lymphocyte proliferation in the peripheral blood mononuclear cells of RA patients compared to normal controls. Interestingly, CD14 cocktails from RA patients provide much stronger protection against AICD compared to those from normal controls. The observed soluble survival signal from CD14+ cells is a general phenomenon because CD14 cocktails prevent both phytohaemagglutinin A-p- and anti-CD3-induced AICD. Furthermore, supernatants collected from human dendritic cell cultures also prevent activated lymphocytes from undergoing AICD. The data implicate an important role of the CD14+ cell and its secreted form of survival signal in the pathogenesis of RA. [ABSTRACT FROM AUTHOR]

extracellular matrix molecule in the thymus, in the cell death induced by activation via the T-cell antigen receptor. FN alone did not increase cell death in murine thymocytes above the baseline level, but it significantly enhanced the cell death induced by fixed anti-CD3 monoclonal antibody (mAb), especially when a high concentration of anti-CD3 mAb was used. DNA fragmentation increased in parallel with cell death, indicating that cell death was a result of the apoptosis. Fluorescence-activated cell sorter (FACS) analysis revealed that the activation-induced cell death (AICD) caused by anti-CD3 mAb alone, or by a combination of anti-CD3 mAb and FN, occurred selectively in CD4+ CD8+ thymocytes. Very late activation antigen (VLA)-4 and VLA-5 are two major ligands to FN on thymocytes. The expression of both ligands was investigated at different stages of thymocyte development. VLA-4 was predominantly expressed at the CD4- CD8- stage, and thereafter the expression was reduced, whereas VLA-5 was constantly expressed during maturation. Furthermore, the enhancing effect by FN was inhibited in the presence of the Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) peptide but not in the presence of the connecting segment-1 (CS-1) peptide, suggesting that enhancement of AICD observed in CD4+ CD8+ thymocytes is mediated through VLA-5. [ABSTRACT FROM AUTHOR]

Deoxyspergualin (DSG) has been found to have an antitumour and immunosuppressive activity. However, the precise mechanism of action of DSG has not been clarified. We have used its analogue, methyldeoxyspergualin (MeDSG) for in vitro culture studies of DSG since it shows good stability in aqueous solution and retains strong immunosuppressive activity. In the present study, we found that MeDSG inhibited proliferation of rapidly dividing murine T-cell hybridomas, resulting in cell death. The cell death was accompanied by chromatin condensation and DNA cleavage at the linker regions between nucleosomes. Furthermore, MeDSG induced a reduction in mitochondrial transmembrane potential. When murine thymocytes were treated with MeDSG for 48 hr, a slight increase of DNA fragmentation was constantly observed, and selective depletion of CD4- CD8- cells was noticed. In contrast, CD4+ CD8+ cells were hardly affected. Moreover, splenic T-cells are resistant to MeDSG-induced apoptosis, as evaluated by measuring DNA cleavage. Our findings may account for the immunosuppressive and antitumour properties of DSG which were described in a number of previous studies. [ABSTRACT FROM AUTHOR]

Isolated immune complexes from sera of 49 out of 67 human immunodeficiency virus-1-positive (HIV-1+) patients (CIC-HIV+), composed of anti-HIV-HIV-Ag, could induce apoptosis on normal phytohaemagglutinin (PHA)-activated lymphocytes. DNA degradation was detected by propidium iodide staining. This activity is directed against CD4+ lymphocytes as demonstrated by double binding of CIC-HIV+ and anti-CD4 on apoptotic cells. Expression of Fas antigen is prior to apoptotic phenomena. CIC-HIV+ apoptosis inducers belong mainly to asymptomatic HI V-infected patients, indicating that immune complexes from these patients can destroy CD4+ lymphocytes. [ABSTRACT FROM AUTHOR]

Platelet cytotoxicity was examined in vitro using various tumour cell lines as target cells. Thrombin-activated platelets as well as unstimulated platelets exerted a cytotoxic effect on some tumour cell lines including K562, KU812, LU99A and KG1, but other tumour cell lines including U937. MIA PaCa-2 and MOLT-4 were completely insensitive to this effect. Electron microscopic examinations showed that unstimulated platelets adhered to target K562 cells but thrombin-activated platelets did not. Morphological changes of K562 cells induced by unstimulated and thrombin-activated platelets were indistinguishable. When platelets and K562 cells were co-cultured in the same vessel but were prevented from coming into direct cell-to-cell contact by means of a membrane barrier, cytotoxicity of unstimulated platelets was completely blocked but that of thrombin-activated platelets was still detectable. However, no cytotoxic activity to K562 cells was detected in the supernatants obtained after stimulation of platelets with either target cells or thrombin for 4 hr. Extracellular Ca2+ ion was not required for the platelet-mediated cytotoxicity. Esterase inhibitors SBTI and TPCK had no effect on the formation of platelet-target cell adhesion but inhibited the cytotoxicity of unstimulated platelets. In contrast, the inhibitors had no effect on the cytotoxic activity of thrombin-activated platelets. These results suggest that direct contact between platelets and target cells is essential for unstimulated platelets but not for thrombin-activated platelets to exert cytotoxicity and that some esterases play a role in the cytotoxic process of unstimulated platelets. They also provide evidence that some cytotoxic effectors are soluble and easily inactivated factors liberated by activated platelets. Our findings indicate that platelets may be one of the cytotoxic effector cells against certain neoplasia. [ABSTRACT FROM AUTHOR]

Cyclosporin A (CsA) is reported to inhibit programmed cell death. We confirmed this by using T-celI hybridomas which are inducible to programmed cell death by activation with immobilized anti-CD3 antibody or with anti-Thy 1.2 antibody. Cell death and DNA fragmentation, characteristic features of programmed cell death, were almost completely blocked by CsA or FK506. To investigate whether CsA inhibits only the cell death through the signals via the TCR/CD3 complex or all of the programmed cell death induced by various reagents, we further established CD4+8+ thymic lymphomas which result in programmed cell death after activation with calcium ionophore, dexamethasone, cyclic AMP or anti-CD3 antibody. It was revealed that CsA could block only the cell death mediated by the TCR/CD3 complex. For the clarification of the site of action of CsA, Ca2+ influx and endocytosis of receptors after stimulation with anti-CD3 antibody were monitored in the presence of CsA, and no significant effects of CsA were observed. Furthermore, prevention of cell death was examined by adding CsA at various periods of time after initiation of culture. CsA was found to exert its effect even when added after 4 h of cultivation, and the kinetic pattern of suppression was similar to that of the suppressive effect on IL-2 production. These observations indicate that in the events of programmed cell death, the major site of action of CsA will not be the inhibition of the immediate membrane events after activation of the TCR/CD3 complex but rather the interference in the function of molecules that transmit signals between membrane events and the activation of genes in the nucleus. [ABSTRACT FROM AUTHOR]

Antibodies to a number of cell surface antigens expressed on mouse spleen cells were tested for their ability to inhibit antibody-dependent cell-mediated cytotoxicity (ADCC) of antibody-coated sheep erythrocytes (Ab-SE) in the absence of complement. Of the antibodies tested, only the antisera to Ly- 5 and H-2 antigens significantly inhibited ADCC by spleen cells reactive with those antisera. Inhibition by Ly-5 antisera was shown to be allotype-specific by inhibition experiments using C57BL/ 6-Ly-5.1 (B6-Ly-5.1) and congenic C57BL/6-Ly-5.2 (86-Ly-5.2) mice. Inhibition by Ly-5.1 antiserum appeared not to be due to competition for the Fc receptor (FcR), since in mixing experiments 'third-party' thymus cells treated with Ly-5 antiserum did not inhibit the cytotoxic activity of untreated cells. In comparing inhibition induced by antisera to H-2 and Ly-5 antigens, Ly- 5.1 antiserum was more inhibitory at nearly every dilution tested. In addition, F(ab')2 fragments of Protein A-purified Ly-5.1 antibody were inhibitory to RALR/c spleen effector cells in ADCC of Ab- SE, whereas F(ab')2 fragments of H-2 antibodies had no effect. Because ADCC of tumour cells may share a common lytic mechanism with ADCC of erythrocytes, several antisera to cell surface antigens found on spleen cells were tested for inhibition of ADCC to antibody-coated P815 tumour cells (Ab-P815). As seen in ADCC to Ab-SE, anti-Ly-5.1 was a more potent inhibitor than antibody against either H-2k or H-2d antigens. The results are discussed in the light of the ability of Ly-5 antisera to inhibit various types of cell-mediated killing. [ABSTRACT FROM AUTHOR]

In order to explore the role of glutathione in cell-mediated cytotoxicity, we have examined the effect of the sulphydryl-reactive and glutathione-depleting agent 2-cyclohexene- 1 -one on antibody- dependent cellular cytotoxicity, spontaneous cell-mediated cytotoxicity, and cell-mediated lympho- lysis by human peripheral blood mononuclear cells. 2-Cyclohexene- 1 -one significantly inhibited (P < 0.001) both antibody-dependent and spontaneous cell-mediated cytotoxicity using three different cell-line targets, at three different killer: target cell ratios (10: 1,25: 1 and 50: 1). Using K-562 cell-line targets, spontaneous cell-mediated cytotoxicity was inhibited by 2-cyclohexene-1-one with an ID50 of 0.71 × 10-4 M-3.98 × 10- M, while antibody-dependent cellular cytotoxicity was less sensitive to inhibition, and required slightly higher concentrations of 1.48 × 10-4 M-3.98 × 10-4 M to achieve 50% inhibition. Similar results were seen with human colon tumour cell-line and Chang liver cell-line cells as targets. Maximal inhibition occurred when 2-cyclohexene-1-one was added to the cytotoxicity assay 60 mm prior to, at the start of, or within the first 60 mm of a 4-hr assay; inhibition of cytotoxicity occurred with pretreatment of effector cells; and no inhibition of cytotoxicity was observed with pretreatment of target cells. Both the allogeneic mixed leucocyte reaction and cell- mediated lympholysis were also significantly inhibited (P < 0.001) by 2-cyclohexene-1-one. These studies demonstrate that 2-cyclohexene-1-one is an effective inhibitor of cell-mediated cytotoxicity and suggest that glutathione, specific glutathione-protein interactions, or protein-bound sulphydryl groups are involved in allowing cells to carry out cytolysis. [ABSTRACT FROM AUTHOR]

As a model for the recognition of effete cells by their viable neighbors, BALB/c mouse thymocytes were coincubated with isologous peritoneal macrophages. The macrophages bound preferentially to thymocytes undergoing apoptosis, a mode of death induced in these cells by treatment with the glucocorticoid hormone methyl-prednisolone. Binding occurred in the absence of serum and was inhibited by N,N'-diacetyl chitobiose, N-acetyl glucosamine and, to a lesser extent, by N-acetyl galactosamine and n-galactose. L-fucose, 0-mannose and N-acetyl neuraminic acid had no effect. The results suggest the presence of lectin-like molecules on the surface of the macrophage that recognize changes in the cell-surface carbohydrate of the apoptotic cell. The pattern of inhibition of binding by monosaccharides differs from that of previously described endogenous mammalian lectins. [ABSTRACT FROM AUTHOR]

Antibody-dependent cell-mediated cytotoxicity (ADCC) carried out by fresh and precultured peripheral blood mononuclear cells (PBMC) was compared. The results indicate that the cytotoxic capability was decreased in precultured PBMC, probably due to the effect of suppressor cells. The depletion of adherent cells before preincubation eliminated inhibitory effects, suggesting that the suppressor activity resided in this cell fraction. In addition, supernatants from adherent cell cultures were also able to suppress ADCC of non-adherent PBMC. Normal ADCC values were restored by supplementing the reaction medium with cycloheximide (Cy) 1 × 10-3 M. The enhancing effect of Cy was exerted upon whole and adherent PBMC, while the opposite effect was observed when ADCC was carried out by non-adherent cells. The fact that Cy increased ADCC activity by precultured PBMC might rule out the possibility that suppression could be ascribed to trivial factors such as cell death, overcrowding or steric hindrance. The results presented in this report support the premise that ADCC is under active immunoregulation. [ABSTRACT FROM AUTHOR]

The effect of neonatal thymectomy at various times after birth (Tx-1, Tx-7) on effector and suppressor I cells responsible for cell-mediated cytotoxicity (CMC) for allogeneic antigens was deter- mined. Following in-vitro primary mixed lymphocyte cultures, in the absence of T-cell growth factor (TCGF), alloreactive CMC was not detected in spleen cells of Tx-1 mice, but was detected in spleen cells of Tx-7 mice at as high levels as in those of sham-operated mice. However, in the presence of TCGF, as much alloreactive CMC was detected in spleen cells of Tx-1 mice as in those of Tx-7 mice. Furthermore, TCGF production was not detected in spleen cells of Tx-1 mice but was detected in those of Tx-7 mice. In in-vivo experiments, inhibition of allogeneic tumour growth and CMC in spleen cells showed the same pattern as in in-vitro experiments. These results sup- port the concept that the reduction of CMC in Tx-I mice might be due to a defect in helper function (TCGF-producing capacity) rather than to a defect in cytotoxic T lymphocytes and/or cytotoxic T lymphocyte precursors. Alloreactive suppressor T cells could not be induced in spleen cells of Tx-1 mice but were induced in spleen cells of Tx-7 mice. Therefore, it was suggested that alloreactive suppressor T cells require the presence of the thymus for 7 days after birth in their development. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cell activity was found in the various lymphoid compartments of the normal guinea-pig, prominent in the spleen and absent in the thymus. Oestrogen treatment. which increased the Kurloff cell population in blood, spleen and thymus, did not alter NK cell activity in blood and spleen but markedly augmented the lytic capacity of the thymus. Resetting reactions and selective depletion studies in normal and oestrogen-treated animals revealed the NK cells to belong to a small population of E+ Kurloff cells, some of which were Fe+ and others apparently Fe+. Some of these natural killer cells in the spleen also had receptors for C3 and carried Ig (probably cytophilic). ln the lymph nodes, however, the NK cells were found to he E + lymphocytes, again some of which were Fe+ and others Fe+. [ABSTRACT FROM AUTHOR]

Isolated P815 karyoplasts are up to four times more susceptible to lysis by T cells than intact cells, suggesting that the target cell nucleus or a nuclear associated structure may be particularly sensitive to cell-mediated cytotoxicity. Cytoplasts showed variable susceptibility. The morphological changes seen by time-lapse cinematography show that the first change seen with intact cells is a burst of zeiosis (membrane blebbing), whereas neither cytoplasts nor karyoplasts exhibit zeiosis. These observations suggest that zeiosis results from changes in the cytoskeletal system. This is discussed in relation to the possibility that T cells kill target cells by causing physical damage to a critical organelle inside the cell rather than to the membrane itself. [ABSTRACT FROM AUTHOR]

Electron micrographs of material fixed during the first 10 mm of a T-cell cytotoxic system showed T-cell projections and T-cell burrowing into target cells. These observations were made possible by using a system with a very high rate of killing. The projections vary in shape and size, and can push deeply into the target cell, distorting organelles in their path, including the nucleus. The projections contain fine fibrillar material, to the exclusion of organelles. They push the target cell membrane in front of them to form pockets approximating to the shape of the projection. Areas of close contact occur between the projections and the target cell membrane, particularly at the leading edges. The likelihood that these projections develop as a result of Contact with specific antigen, and are involved in the Cytotoxic mechanism is discussed. [ABSTRACT FROM AUTHOR]

[75Se]L-selenomethionine can be employed as a label for following lymphocytes in vivo. Its properties are broadly similar to those of 51Cr with regard to uptake, release of the isotope on cell death and reutilization; thus relatively high levels of 75Se in lymphoid tissue indicate the presence of viable labelled cells. It differs from 51Cr in that active release of selenium occurs from the labelled cells when the ambient cell concentration is low. No significant reutilization of leaked label occurs. Leakage of 75Se label occurs in vivo; this differs in the spleen and lymph nodes. Evidence is presented to suggest that 75Se losses reflect the transit times of cells through lymphoid organs. [ABSTRACT FROM AUTHOR]

Fourteen days after injection with Detroit-6 cells (a human cell line) rats have high titres of antibody capable of inducing cytotoxicity towards Detroit-6 cells in normal spleen cells. At the same time, the spleen cells from the injected rats are cytotoxic for Detroit-6 cells in vitro. However, killing by allergized spleen cells is apparently not entirely antibody induced, since heterologous anti-thymocyte sera (absorbed with rat bone marrow cells) inhibit target cell killing by spleen cells from injected rats but do not appreciably inhibit killing of antibody-coated target cells by normal spleen cells. Wistar spleen cells 'activated' by transfer into irradiated August rats are cytotoxic for August hepatoma cells. This cytotoxicity is also inhibited by the absorbed anti-thymocyte sera. It is suggested that the cytotoxicity of spleen cells in vitro, in both these allogeneic and xenogeneic systems, is mediated by thymus-derived (T) cells. [ABSTRACT FROM AUTHOR]

The aim of the experiments was to find a T cell-mediated cytotoxic reaction where genetically determined low responsiveness is under the control of recessive genes. The T cell-mediated immune response to DBA/2 mastocytoma cells P 815-X2 in different inbred strains, F1 hybrids and congenic resistant strains of mice was determined using the 51Crk-release method. Two types of low responsiveness were found. The first already well documented type is characterized by dominance of low responsiveness in genetical analysis. It is due to tolerance because of the identity of the H-2 linked specificities of the recipient and of DBA/2 (H-2d) mice from which the turnout is derived. The second and new type of low responsiveness in T cell-mediated immunity was found in DBA/1 mice. In this strain low responsiveness is inherited as a recessive trait. The cytotoxic response of DBA/1J mice against the C57B1/6 lymphoma EL 4 is normal. Thus, their low responsiveness is restricted to a limited number of membrane determinants. [ABSTRACT FROM AUTHOR]

A method for the quantitation of cytotoxic action of antiserum and complement is described, measuring the incorporation of trypan blue into Ehrlich ascites tumour cells. The incorporation of the dye into the cells in the presence of antiserum and complement was maximum at ionic strength between 010 and 015, and decreased with increasing ionic strength higher than 015. The permeability barrier of the cell against the dye was stable at pH between 7.2 and 7.4. The cytotoxic reaction required Mg ++ and Ca++ ion, but was inhibited with concentrations higher than 5 mM Mg+ + and 1 M NCa. The incorporation of the dye in the presence of antiserum and complement was more rapid with increasing concentrations of the dye, and depended on temperature. From these findings we obtained optimal condition for the assay of cytotoxic antiserum. [ABSTRACT FROM AUTHOR]

Experiments are described using the reactive lysis system on phospho-lipid dispersions to study the terminal phases of complement lysis. It has been found that, both on lecithin and on sphingomyelin-cholesterol liposomes, marker release and characteristic EM lesions can be found upon the sequential activity of C567 and C8 and C9 and that for both these parameters of lysis the action of C8 and C9 as well as of C567, are required. Lysis of liposomes is accompanied by the appearance of traces of the products of phospholipase activity in the supernate but it is believed that these represent the activity of contaminating enzymes and are the consequence and not the cause of lysis. However the possibility that lysis could be due to lipolytic activity cannot be totally excluded because of the negligible hydrolysis theoretically needed to form lesions. [ABSTRACT FROM AUTHOR]

Reports that balancing cell death and proliferation plays a key role in the maintenance of homeostasis and the prevention of cancer in all multicellular organisms. Functions of pro-apoptotic and antiapoptotic members; Number of exons that consists the gene; Assessment on the functional importance of B-Myb in the regulation of the bcl-2 gene.