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Query: UMLS:C0009443 (cold)
 92,137 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intratumoral heterogeneity has been proposed as a possible basis for immunotherapeutic failure when tumor-specific agents such as tumor infiltrating lymphocytes (TIL) are employed for cancer therapy. To examine this issue, highly specific oligoclonal MHC class I-restricted cytolytic TIL grown in bulk culture from patient 397 were used to immunoselect a TIL-resistant variant tumor from the autologous cultured melanoma line 397-mel. Four cycles of immunoselection produced tumor 397-R4, a variant completely resistant to 397 TIL but not to allogeneic LAK cell lysis in 4-h 51Cr release assays. By flow microfluorometry analysis, this tumor variant had not lost MHC molecules, adhesion molecules, or a variety of tumor-associated Ag expressed by the parent tumor but showed decreased expression of many Ag examined. Failure of 397-R4 to cold target inhibit TIL lysis of 397-mel suggested that cell-surface modification was at least one mechanism causing TIL resistance. The inherent lysability of 397-R4 was equal to 397-mel, as confirmed by lectin-dependent cellular cytotoxicity, lysis by non-MHC restricted allogeneic TIL, and lysis by a second line of 397 TIL grown independently from tumor 397. Treatment of 397-R4 with IFN-alpha or IFN-gamma, +/- TNF-alpha for 72 h before cytolytic assays enhanced TIL lysis of this target slightly, and enhanced surface expression of MHC class I and II molecules and the adhesion molecule ICAM-1. The resistant phenotype of 397-R4 was evident in all clones of 397-R4 examined and has been maintained in serial culture for over 13 mo and through passage in nude mice, suggesting that such stable tumor variants may provide an in vivo escape mechanism from specific immune reagents such as TIL. Evolving patterns of TIL culture clonality over time, as well as the spontaneous emergence of different clones in two long term TIL cultures grown under identical conditions from the same source of cryopreserved tumor, were documented by analyzing TCR gene rearrangements and suggest that TIL from different culture passages or lines may be used to overcome resistant tumor subpopulations.
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PMID:Immunoselection of a human melanoma resistant to specific lysis by autologous tumor-infiltrating lymphocytes. Possible mechanisms for immunotherapeutic failures. 216 May 3

Two murine monoclonal antibodies (MAbs) against Aspergillus fumigatus were produced and characterized. Splenocytes from cell wall-immunized BALB/c mice were fused with SP2/0 myeloma cells. The hybridomas were screened with a cold alkali (CA) extract of mycelium containing protein, mannose, and galactose, and two MAbs of the immunoglobulin M class were purified from ascites fluid. MAbs 1 and 40 were characterized by double immunodiffusion against CA antigen, indirect enzyme immunoassay with mannans of Candida albicans serotypes A or B or Candida tropicalis, indirect immunofluorescence with C. albicans- or A. fumigatus-infected tissues, indirect immunofluorescence with smears of other pathogenic fungi, Western blotting (immunoblotting) with the lectin concanavalin A or BS-1 from the seeds of Bandeirea simplicifolia, and immunoelectron microscopy. MAb 1 did not cross-react with Candida mannan and recognized a periodate-sensitive, pronase- and heat-resistant epitope in CA antigen and three mannose- and galactose-containing components (80, 62, and 49 kilodaltons) of a mycelial homogenate. Immunoelectron microscopy demonstrated binding of MAb 1 to the inner cell wall and intracellular membranes of hyphae and conidia of A. fumigatus. Circulating antigen was detected in experimental invasive aspergillosis by inhibition enzyme immunoassay with MAb 1 and CA antigen. MAb 40 was a nonprecipitating antibody cross-reactive with Candida species, and competition for an epitope located diffusely in the cell wall of A. fumigatus hyphae was demonstrated by incubating MAb 40 with mannan of C. albicans serotype A. These results suggest that MAb 1 recognizes immunodominant oligogalactoside side chains of A. fumigatus galactomannan, while MAb 40 binds to mannopyranosyl side chains common to A. fumigatus galactomannan and C. albicans mannan.
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PMID:Production and characterization of monoclonal antibodies to cell wall antigens of Aspergillus fumigatus. 219 59

Glycosidase enzyme digestion in combination with postembedding lectin cytochemistry was used to study the carbohydrate composition of axonally transported glycoproteins. A cold block procedure for the interruption of axonal transport was employed to increase selectively the population of anterograde moving components on the proximal side of the transport block. Electron-microscopic observations revealed that a cold block applied to the sciatic nerve of an anesthetized rat produced an increase in axonal smooth membrane vesicles at a site directly proximal to the cold block. Postembedding lectin cytochemistry of the sciatic nerve demonstrated a substantial increase in concanavalin A (Con A), wheat germ agglutinin (WGA), and succinylated WGA binding sites in axons directly proximal to the cold block. Endoglycosidase H (endo H) digestion prior to lectin cytochemistry characterized a large population of the axonally transported Con A binding sites as polymannose and/or hybrid N-linked oligosaccharides (endo H-susceptible). A distinct population of neuraminidase-resistant WGA binding sites was also found in axons directly proximal to the transport block. The concomitant increase in smooth membrane vesicles and lectin binding sites in axons at the transport block supports the hypothesis that a system(s) of smooth membrane inside the axon is involved in the transport of glycoproteins from the cell soma to their cell surface destinations. Results of glycosidase digestions and lectin cytochemistry experiments suggest that many of the axonally transported glycoprotein carbohydrates are polymannose and/or hybrid N-linked oligosaccharides. This observation is especially interesting in relation to our previous reports, which indicated that most lectin binding sites on the neuronal cell surface are composed of complex oligosaccharides.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analysis of the carbohydrate composition of axonally transported glycoconjugates in sciatic nerve. 242 59

Ld/Q7d, a hybrid molecule consisting of alpha-1 and alpha-2 domains from H-2Ld and alpha-3 and carboxy-end components from Q7d, was expressed on the surface of CRL-3A rat liver cells. This molecule retained serologic H-2Ld epitopes. The Ag is attached to the cell membrane through a phosphatidyl-inositol linkage, characteristic of Qa-2 molecules. Both bulk cultured and cloned H-2Ld alloreactive CTL as well as H-2Ld restricted vesicular stomatitis virus-specific CTL lyse CRL-3A cells which express H-2Ld but show little or no lytic activity on cells which express the Ld/Q7d hybrid. These cells also fail to act as cold target competitors for alloreactive anti-H-2Ld CTL. However, cells expressing Ld/Q7d are not resistant to CTL mediated lysis because they can be killed in the presence of lectin. These data indicate that recognition of polymorphic class I CTL epitopes in the alpha-1 and alpha-2 domains are influenced by the structure of the carboxy-end of the molecule.
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PMID:An H-2Ld hybrid molecule with a Qa-2 alpha-3 domain and phosphatidyl-inositol anchor is not recognized by H-2Ld-specific cytotoxic T lymphocytes. 246 90

The antigen-independent binding of CD4+ T-lymphoblasts by alveolar and peritoneal macrophages and splenic dendritic cells (DC) was compared. DC formed clusters with T-lymphoblasts within 30 min at 37 degrees C, whereas alveolar and peritoneal macrophages did not. Antigen-independent binding developed between macrophages and CD4+ blasts by 4 h at 37 degrees C. Binding by alveolar macrophages was trypsin sensitive, magnesium dependent, serum independent, and cold insensitive, whereas binding by DC required serum and was inhibited by cold. Cluster formation (cell aggregates greater than 250 microns 2) by macrophages and CD4+ blasts was increased by interferon-gamma and phorbol esters, but diminished by lipopolysaccharide. However, each of these factors increased cluster formation by blasts with DC. Efforts to promote antigen-independent binding of T cells by Ia+ macrophages did not alter their poor accessory cell capacities. The role of cluster formation in accessory cell activities was examined. Inhibitors of DC clustering, including trypsin, paraformaldehyde, and tunicamycin, abrogated the ability of DC to support antigen presentation and lectin-mediated proliferation. It is concluded that rapid antigen-independent binding to T-cells is a distinct property that is restricted to DC. Exposure to LPS may down regulate nonproductive binding of T-cells to alveolar macrophages. Our data further suggest that accessory cell activities in the rat are not a function of alveolar macrophages and may be limited to specialized Ia+ cells of dendritic lineage.
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PMID:Antigen-independent binding of T-cells by dendritic cells and alveolar macrophages in the rat. 249 72

We observed that lymphokine-activated T lymphocytes, obtained in short- and long-term cultures following stimulation with recombinant interleukin-2 (rIL-2), are resistant to cell-mediated cytotoxicity. In particular, lymphokine-activated killer (LAK) cells do not undergo self-lysis or lysis by alloreactive cytotoxic T lymphocytes (CTL), in line with recent reports concerning CTL clones. Similar findings were further confirmed in a lectin-dependent cell cytotoxicity assay. LAK cell lysis resistance was not due to an inability to recognize itself, since inactivated LAK cells used as cold competitors inhibited tumor cell lysis in a dose-dependent manner. In contrast, the addition on Day 0 of irradiated LAK cells or alloreactive CTL, as well as a CTL clone having LAK-like activity to rIL-2-stimulated cultures abrogated or strongly reduced LAK cell generation. Therefore, LAK cell precursors were most likely susceptible to the lytic activity of differentiated cytotoxic cells, as no inhibition was detected when cell to cell contact was prevented by using a diffusible chamber culture system. These findings, on the whole, suggest that the emergence of the lysis-resistant phenotype is most likely the result of a selective process occurring in vitro that leads to the elimination of lysis-susceptible lymphocytes present in culture.
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PMID:Resistance of lymphokine-activated T lymphocytes to cell-mediated cytotoxicity. 278 17

We have studied the suppressive ability of human cord blood lymphoid cells in a three-days mixed lymphocyte culture proliferation assay stimulated by mitogen. Sex chromosomes served as markers for dividing cord (male) or maternal cells. Three distinct mitogenic agents were used in the co-cultures: the mitogenic lectin PHA, the anti-CD3 monoclonal antibody OKT3, and 12-0-tetradecanoyl-13-acetate (TPA), a direct activator of protein kinase C. With all mitogens we observed significant, non-specific suppression of maternal/adult cell division. However, three separate levels of suppression were evident. PHA-stimulated co-cultures always showed the highest amount of cold suppressor activity (mean +/- SEM: 64.9 +/- 3.9). The mean suppression in OKT3- and TPA-stimulated co-cultures was 34.7 +/- 6.0 and 22.0 +/- 4.1%, respectively. Furthermore, indomethacin, a prostaglandin (PG) synthetase inhibitor, reduced by 41% the suppression in PHA-driven co-cultures, whereas having no significant effect on the corresponding OKT3-driven co-cultures. Our results indicate the existence of an indomethacine-sensitive, PG-dependent mechanism and a separate, indomethacine-resistant, mechanism of cord cell suppression.
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PMID:Distinct mitogens reveal different mechanisms of suppressor activity in human cord blood. 297 39

Thirteen cases of angiosarcoma of the face and scalp have been examined using immunohistochemistry and electron microscopy. Endothelial cell markers have been employed in an immunoperoxidase technique on tissue that has either been routinely processed, periodate-lysine paraformaldehyde fixed (PLP) and cold processed, or fixed in methacarn. A consistent pattern of endothelial cell labeling was only achieved in the PLP fixed tissue. In this fixative the angiosarcomas were factor VIII related antigen negative, Ulex europaeus lectin positive, laminin positive, unlabelled by the monoclonal antibody PAL-E, and positively labelled by the monoclonal antibody EN4. Ultrastructural examination of four cases showed evidence of vascular lumina in all tumours. Weibel-Palade bodies were seen in only one case but three tumours showed some evidence of tight junction formation and marginal folding. Thus, our cell marker studies can be interpreted as consistent with a lymphatic derivation for this type of angiosarcoma but in contra-distinction the ultrastructural studies showed tumour channels with features suggestive of blood vessel differentiation.
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PMID:The histogenesis of angiosarcoma of the face and scalp: an immunohistochemical and ultrastructural study. 310 87

Murine splenocytes incubated for 3 to 4 days with the lymphokine, IL-2, acquire the ability to mediate the lysis of a wide variety of fresh tumor targets in short term chromium release assays. We undertook these studies to examine the lysis of splenocyte blasts by these lymphokine-activated killer (LAK) cells, to help gain an understanding of the mechanisms of target cell recognition. Allogeneic blast targets but not syngeneic blasts are highly lysable by LAK effector cells. By using congenic mice, we have shown that only the H-2 haplotype, and not other differences, determines the recognition and lysis of a blast target cell. Both Con A- and LPS-induced allogeneic splenocyte blasts are lysed and thus lectin-induced binding of effectors and targets is unlikely to be responsible for this effect. By using in vivo antibody depletion experiments, we showed that different populations of effector cells mediate the lysis of tumor cells and allogeneic blasts. Furthermore, we observed that the lysis of a susceptible blast can be inhibited only by like cold blasts of the same haplotype. These results suggest that there is a separate population of LAK cells responsible for the lysis of each type of blast target cell. Though syngeneic blasts were not lysed by LAK cells, TNP modification of syngeneic blasts converted them into cells that were recognized and lysed by LAK cells. In cold target inhibition studies, the lysis of fresh syngeneic tumor was not inhibited by TNP-modified syngeneic blasts. Similarly, the lysis of TNP-modified syngeneic blasts was not inhibited by fresh tumor. By using in vitro antibody depletion, we determined that TNP-modified blasts are lysed by LAK cells with Thy-1+ precursors, in distinction to the Thy-1- precursors involved in tumor cell lysis. Elimination of the Thy-1+ cells at the precursor stage completely abrogated the lysis of blasts but did not diminish the lysis of tumor cells. We conclude that IL-2 promotes the growth of numerous populations of effector cells with Thy-1+ precursors that have a narrow range of specificity, in contrast to the broad lytic ability for fresh tumor mediated by LAK cells with Thy-1- precursors.
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PMID:Heterogeneity of lymphokine-activated killer cells induced by IL-2. Separate lymphoid subpopulations lyse tumor, allogeneic blasts, and modified syngeneic blasts. 325 3

Three properties related to the erythrocyte membrane skeleton are found to be altered after the binding of concanavalin A (Con A) to erythrocytes or their isolated membranes. Con A binding to normal erythrocytes imparts resistance to heat (49 degrees C)-induced fragmentation of the cells. The fragmentation, due to denaturation of spectrin at 49 degrees C, is prevented by Con A in a dose-dependent manner, but levels off at concentrations of Con A in excess of 100 micrograms/ml. The binding of Con A to ghosts isolated from normal, trypsin- or Pronase-treated cells prevents (completely or substantially) the elution of the skeletal protein complex when the membranes are extracted under low-ionic-strength conditions in the cold. The Con A-agglutinated membranes of trypsin- and Pronase-treated, but not normal, cells show cross-linking of skeletal proteins and band 3 with dimethyl adipimidate, a 0.86 nm (8.6 A)-span bifunctional reagent. The extent of cross-linking is greater in the Pronase-treated membrane than in the less-agglutinable trypsin-treated membranes. The results show that, after Con A has bound, rearrangements occur in the membrane that alter properties of the skeletal proteins. Additionally, redistribution of the skeletal proteins and the Con A receptor occurs in the lectin-agglutinated membranes.
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PMID:Concanavalin A binding to human erythrocytes leads to alterations in properties of the membrane skeleton. 329 34


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