1,721,058 research outputs found
Lewis lung carcinoma (3LL) cells treated in vitro with ultraviolet radiation show reduced metastatic ability due to an augmented immunogenicity
No full textThe metastatic ability of 3LL tumor following in vitro irradiation with ultraviolet (u.v.) light was studied. Tumor cells were exposed to two courses of u.v.-irradiation (3LL X 2u.v. cells) and after two weeks of culture they were inoculated intravenously (i.v.) into syngeneic mice. These cells produced significantly fewer pulmonary metastases than the untreated population. In addition, intrafootpad (i.f.p.) injections of 3LL X 2u.v. cells into immunocompetent animals induced tumors only in 40 per cent of recipients. Interestingly, in normal mice with progressively growing 3LL X 2u.v. tumors, the formation of spontaneous pulmonary metastases was prevented, whereas metastatic foci were observed in 70 per cent of the nude recipients. The metastatic properties of u.v.-treated tumor cells were further analysed by using individual clones with varying immunogenicity. We found that variants with augmented immunogenicity also showed a parallel decrease in metastatic potential. Studies on H-2 antigen expression in different clones revealed that immunogenic and low metastatic variants expressed levels of H-2 antigens higher than the tumorigenic and metastatic clones. Finally, by using cyclophosphamide (Cy) treatment and adoptive transfer of immune spleen cells were able to eradicate macroscopic 3LL pulmonary metastasis. These results demonstrate that the decrease of metastatic ability in u.v.-treated cells was mainly due to an increase in their immunogenicity and H-2 antigen expression
Induction of highly immunogenic variants of Lewis lung carcinoma tumor by ultraviolet irradiation.
No full textThis study was undertaken to determine whether in vitro treatment of Lewis lung carcinoma (3LL) cells with ultraviolet (UV) radiation could increase their immunogenicity. Tumor cells were irradiated with UV light from a germicidal lamp (254 nm; UV-C) at a dose of 720 J/sq m. After 2 weeks of culture, the surviving cell population was cloned by limiting dilution. Cell suspensions of each clone were injected intrafootpad in C57BL/6 mice at a dose of 2.5 X 10(5) cells per mouse. Eighty independent clones were tested. Fifty-one clones showed decreased tumorigenicity and failed to grow in 20 to 95% of immunocompetent mice, whereas they produced tumors in 100% of irradiated (550 R) and athymic nude mice. These clones were designated "tum-" (nontumorigenic) clones. In contrast, all 25 clones selected from the untreated parental 3LL induced progressively growing tumors in 100% of the mice. After two courses of UV treatment, the uncloned 3LL population was rejected in 45% of inoculated mice. Mice rejecting an inoculum of a tum- clone were completely resistant to subsequent challenge with higher doses of the same or unrelated tum- clones. This resistance was fully expressed even after irradiation of immune mice with 550 R. Mice immune to a tum- clone also were able to prevent the growth of various tum+ clones or untreated 3LL tumor cells. When tum- and tum+ clone cells were simultaneously inoculated intrafootpad in opposite legs, rejection of tum- clone resulted also in the prevention of the growth of tum+ clone. Spleen cells of immune mice caused rapid elimination of radiolabeled 3LL tumor cells from the place of their inoculation (intrafootpad) and prevented tumor growth. In an in vitro cytotoxic assay, spleen cells after in vivo and in vitro immunization with tum- clones demonstrated high cytotoxic activity against various tum+ clones and parental 3LL cells, as well as against tum- clones. In addition, parental 3LL tumor cells and tum- cells were similarly able to inhibit cytotoxic activity in the cold target inhibition assay. However, in contrast to tum- cells, 3LL cells were less efficient in in vitro restimulation of cytotoxic activity of immune spleen cells. Therefore, these data suggest that tum-, tum+, and parental 3LL cells share a common antigenic specificity, which is not immunogenic in 3LL cells. UV treatment presumably converted the antigenic determinants present in the 3LL cells into an immunogenic form.This study was undertaken to determine whether in vitro treatment of Lewis lung carcinoma (3LL) cells with ultraviolet (UV) radiation could increase their immunogenicity. Tumor cells were irradiated with UV light from a germicidal lamp (254 nm; UV-C) at a dose of 720 J/sq m. After 2 weeks of culture, the surviving cell population was cloned by limiting dilution. Cell suspensions of each clone were injected intrafootpad in C57BL/ 6 mice at a dose of 2.5 x 105 cells per mouse. Eighty independent clones were tested. Fifty-one clones showed decreased tumori-genicity and failed to grow in 20 to 95% of immunocompetent mice, whereas they produced tumors in 100% of irradiated (550 R) and athymic nude mice. These clones were designated “turn” (nontumorigenic) clones. In contrast, all 25 clones selected from the untreated parental 3LL induced progressively growing tumors in 100% of the mice. After two courses of UV treatment, the uncloned 3LL population was rejected in 45% of inoculated mice. Mice rejecting an inoculum of a turn- clone were completely resistant to subsequent challenge with higher doses of the same or unrelated turn- clones. This resistance was fully expressed even after irradiation of immune mice with 550 R. Mice immune to a turn” clone also were able to prevent the growth of various turn* clones or untreated 3LL tumor cells. When turn” and tum+clone cells were simultaneously inoculated intrafootpad in opposite legs, rejection of turn” clone resulted also in the prevention of the growth of tum+ clone. Spleen cells of immune mice caused rapid elimination of radiolabeled 3LL tumor cells from the place of their inoculation (intrafootpad) and prevented tumor growth. In an in vitro cytotoxic assay, spleen cells after in vivo and in vitro immunization with turn” clones demonstrated high cytotoxic activity against various tum+ clones and parental 3LL cells, as well as against turn- clones. In addition, parental 3LL tumor cells and turn” cells were similarly able to inhibit cytotoxic activity in the cold target inhibition assay. However, in contrast to turn” cells, 3LL cells were less efficient in in vitro restimulation of cytotoxic activity of immune spleen cells. Therefore, these data suggest that turn”, tum+, and parental 3LL cells share a common antigenic specificity, which is not immunogenic in 3LL cells. UV treatment presumably converted the antigenic determinants present in the 3LL cells into an immunogenic form. © 1985, American Association for Cancer Research. All rights reserved
The quest for a vaccine against Helicobacter pylori: how to move from mouse to man?
No full textSeveral lines of evidence from experimental animal models of infection have clearly demonstrated the feasibility of a prophylactic and therapeutic vaccine against Helicobacter pylori. However, comparatively few clinical studies have been carried out to evaluate whether the positive results obtained in animals can be reproduced in humans. The preliminary results obtained with single component, mucosally delivered vaccines have shown very limited results thus far. Very good immunogenicity and safety profiles are now being obtained with parenterally delivered, aluminium hydroxide-adjuvanted multicomponent candidate vaccines. For sure, better vaccine formulations, better antigen preparation(s), better adjuvants, and better delivery systems have to be designed and tested for safety and immunogenicity. These studies are also needed for deciphering those aspects of the effector immune responses that correlate with protection against H. pylori infection and disease
Haemophilus
No full textDescrizione del genere Haemophilus: classificazione, meccanismi patogenetici, manifestazioni cliniche, diagnosi di laboratorio, epidemiologia, terapia e profilassi
Brucella
No full textDescrizione del genere Brucella: classificazione, meccanismi patogenetici, manifestazioni cliniche, diagnosi di laboratorio, epidemiologia, terapia e profilassi
Bordetella
No full textDescrizione del genere Bordetella: classificazione, meccanismi patogenetici, manifestazioni cliniche, diagnosi di laboratorio, epidemiologia, terapia e profilassi
Increase in H-2 antigen expression and immunogenicity of BL6 melanoma cells treated with N-methyl-N'-nitronitrosoguanidine
No full textTreatment of the BL6 melanoma cells in vitro with N-methyl-N'-nitronitrosoguanidine dramatically increased their expression of H-2Kb and H-2Db antigens as well as beta 2-microglobulin but not Class 2 major histocompatibility complex antigens. The treated tumor cells also became immunogenic and were rejected in 70% of syngeneic C57BL/6 recipients, whereas these tumor cells produced progressively growing tumors in 100% of irradiated (550 R) or nude mice. In contrast to the effects of N-methyl-N'-nitronitrosoguanidine treatment, no influence of H-2 antigen expression or tumorigenicity was found when BL6 melanoma cells were treated with 5-azacytidine, phorbol myristate acetate, 5-bromodeoxyuridine, theophylline, or 6-thioguanine. H-2 antigen expression and the tumorigenic properties of 48 individual clones derived from BL6T2 melanoma line and 15 clones from the original BL6 melanoma were investigated. No H-2 antigens were found on the cell surface of the parental BL6 clones, whereas all tum- clones from the BL6T2 line expressed high levels of H-2 antigens. Although four of six tested tum+ clones had high levels of H-2b antigen expression similar to that of tum- clones, they were nonimmunogenic. These data indicate that an increase in major histocompatibility complex antigen expression is essential but not sufficient for the immunogenicity of tumor cells. This conclusion was also supported by the results of interferon treatment of BL6 melanoma cells: this induced an increase in the expression of beta 2-microglobulin and Class 1 H-2b antigens but not an increase in their immunogenicity. Detection of tumor-associated transplantation antigens on the melanoma cells also appeared to be dependent on the level of expression of H-2 antigens. Although tum+ clones grew in normal mice, immune mice were able to prevent the growth of tum+ clones with high levels of H-2 antigens. However, immune mice only partially inhibited the growth of the parental BL6 melanoma or tum+ clones which have low expression of H-2 antigens
A short synthetic peptide fragment of human interleukin-1 beta increases both human and murine natural killer activity
No full textThe effect of a short synthetic fragment of human interleukin-1 beta (hu IL-1 beta) on natural killer (NK) activity was examined. Peripheral-blood mononuclear cells (PBMC) from normal donors showed a significant increase in NK activity against K562 leukemia cells after preincubation for 18 h with the IL-1 peptide. A similar augmentation was not observed after culturing the cells in the presence of hu IL-1 beta. The increase in tumor cell lysis could not be ascribed to a cytolytic activity of the synthetic fragment on target cells, since the peptide caused no direct lysis of various tumor cell lines. Although the peptide enhanced NK cytotoxicity of PBMC, highly purified large granular lymphocytes were not susceptible to its stimulatory effect. The addition to the cultures of antibodies to human interleukin-2 (hu IL-2) completely blocked the peptide-induced boost of NK cytotoxicity, suggesting that IL-2 is mainly involved in the activation process. The ability of the IL-1 peptide to increase NK activity was further confirmed in vivo in the mouse. Cytotoxicity against YAC-1 lymphoma cells, which was very low in the spleen of untreated BALB/c mice, was in fact significantly increased after a single inoculation of the peptide. These data thus indicate that a short synthetic peptide fragment of hu IL-1 beta is able to increase both human and murine NK activity
ALTERATA REATTIVITA’ MACROFAGICA IN CORSO DI INFEZIONE MISTA DA VIRUS E FUNGHI:VALUTAZIONI FUNZIONALI, CITOFLUORIMETRICHE E DI ESPRESSIONE GENICA
No full textBase: I casi clinici di infezioni miste da funghi e virus sono in aumento, soprattutto negli ospiti immunocompromessi.Ciononostante, gli eventi biomolecolari che caratterizzano l’andamento di infezioni polimicrobiche sono tuttora poco conosciuti:scarse sono le conoscenze sulle interazioni che si verificano tra i patogeni e sui derivanti effetti, sinergistici o antagonistici.Nell’ambito del presente lavoro, abbiamo indagato sulla reattività macrofagica nel corso di infezioni miste, sostenute davirus HSV-1 e funghi opportunisti patogeni.Metodi: Sulla base di recenti studi (Cermelli C. et al., 2006), cellule THP-1 infettate per 18 ore con HSV-1 venivano esposte aCandida albicans o Cryptococcus neoformans e quindi saggiate per fagitosi, killing (CFU), marker fenotipici (citofluorimetria)ed espressione genica (microarray di RNA).Risultati: La fagocitosi di entrambi i miceti risulta significativamente aumentata nei monociti infettati da HSV-1 mentre l’attivitàantifungina è diminuita (significativa sopravvivenza e replicazione intracellulare dei due miceti). Al citofluorimetro, celluleTHP-1 infettate mostrano a) significativa downregolazione di TLR2 e TLR4, importanti molecole coinvolte nel riconoscimentodei miceti; b) ridotta espressione di CD38 e CD69, marker di attivazione cellulare; 3) aumento dei marker di apoptosi enecrosi. Il profilo di espressione genica indica un drastico calo (circa il 50%) nella quantità di geni espressi e una modulazionedell’espressione dei geni che comunque restano accesi nelle cellule infettate da HSV-1 rispetto ai controlli (> 7.500 genisovra- o sotto-espressi di almeno 3 volte). In particolare, l’analisi genica per cluster mostra uno spegnimento dei geni coinvoltinella fagocitosi opsonizzata e un aumento dell’espressione di quelli associati alla fagocitosi non opsonizzata. I geni di TLR2and TLR4 risultano downregolati così come molti geni coinvolti nel killing intracellulare.Conclusioni: Questi dati dimostrano che HSV-1 è in grado di alterare la funzione del macrofago fino a renderlo inerme o addiritturapromotore della sopravvivenza e della replicazione del fungo, sottolineando la possibilità di effetti sinergici in vivo nelcorso di infezioni miste
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