摘要:

SUMMARYPrevious work has concluded that murine embryonal carcinoma (EC) cells, the oncogenic stem cells of teratocarcinomas, do not express class‐I,H‐2KorD/Lgene encoded products. Experiments using cell‐mediated lysis, serological and molecular biological approaches show that EC cells do express some major histocompatibility complex (MHC) class I or class I‐like mo

ISSN:1744-3121    

DOI:10.1111/j.1744-313X.1986.tb01094.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYThe RBL‐5 lymphoma has previously been shown to be highly sensitive to natural hybrid resistance, under the control ofH‐2genes at the host level. The present study of the RBL‐5 tumour was focused on progression towards disseminated growth after intravenous (i.v.) inoculation in the syngeneic host and the possible influence of the MHC genes at the tumour cell level. Data are presented to illustrate that there is no obligatory association between reduced H‐2 expression and increased malignancy, and that the opposite may be observed. The wild type RBL‐5 line expressed readily detectable H‐2K and H‐2D products, and a highly malignant subline selected for lung colonizationin vivodid not show any reduction but rather enhanced expression of these antigens. Depending on the inoculum size, this selected subline caused disseminated lymphoma (in the liver, spleen and lungs) at a faster rate or higher frequency of animals than the wild type line. Conversely, a subline selected for reduced H‐2 expressionin vitro, by repeated treatments with antibody and complement, failed to form colonies in any organ after i.v. inoculation, even if the cell dose was increased by more than 100‐fold in comparison with the threshold dose for the wild type tine. This H‐2‐deficient subline was completely resistant to syngeneic RBL‐5 immune cytotoxic T lymphocytes (CTL). Clones isolated during selection of the subline showed different degrees of reduction in sensitivity to H‐2 specific CTL, but an inverse pattern of sensitivity to poly I: C induced natural killer (NK) cells. Selection pressure imposed by NK‐mediated elimination directed preferentially against cells with reduced H‐2 expression may be one explanation of why the gain of histocompatibility antigens is associated with tumour progression in some systems. Another important implication taken up for discussion is that tests for the effect of MHC modulation on tumour growth or immunotherapy require careful experimental design, to cover the action of differ

ISSN:1744-3121    

DOI:10.1111/j.1744-313X.1986.tb01095.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYApproximately 50% of fibrosarcomas induced with methylcholanthrene A were found to be defective in H‐2 expression. In tumours which lack H‐2K antigens, H‐2 gene transfection was used to restore H‐2K expression. Thede novoexpression of H‐2K reduced tumorigenicity and abolished the formation of metastases in syngeneic mice. Expression of H‐2K seems to render the tumour cells immunogenic and leads to effective recognition of the tumour cells by the host im

ISSN:1744-3121    

DOI:10.1111/j.1744-313X.1986.tb01096.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYThe GR9 tumour was induced with methylcholanthrene in a BALB/c mouse, adapted to tissue culture and cloned without any passagein vivo. GR9 clones were typed for H‐2 with three monoclonal antibodies that define H‐2Kd+ Dd, Kdand Ddantigens. A great heterogeneity of H‐2dexpression was found from clones which were Kdand Ddpositive to clones Kdand Ddnegative. These results were confirmed for A7 and B9 clones using immunoprecipitation with anti‐H‐2D.4 and anti‐H‐2K.31 alloantisera and SDS‐PAGE analysis. In addition, the number of chromosomes per cell was heterogeneous amongst the clones, ranging from 38 ± 2 to pseudotetraploid clones which have 75 ± 2 chromosomes.GR9 clones were injected into syngeneic BALB/c mice to measure local tumour growth. We found that the growth correlated with the amount of H‐2 antigen expressed, i.e. clones with low H‐2dexpression were highly malignant while clones with normal H‐2dexpression were highly immunogenic. Finally we found that BALB/c mice immunized against A7 (Kd, Dd‐positive) protected against A7, as expected, but surprisingly also aga

ISSN:1744-3121    

DOI:10.1111/j.1744-313X.1986.tb01097.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYIsoantisera and syngeneic monoclonal antibodies have been produced against A7, a clone derived from a BALB/c methylcholanthrene‐induced tumour named GR9. The antigens defined by the isoantisera and mAbs are widely distributed in a large number of GR9 clones as well as in other tumour cell lines of different aetiology and origin. Two GR9 clones with marked differences in H‐2 expression and syngeneicin vivogrowth (A7, which is H‐2d‐positive and highly immunogenic and B‐9, which is H‐2d‐negative and highly malignant) were selected to further analyse the presence or absence of the antigens recognized by the syngeneic anti‐tumour antibodies.Immunoprecipitation data with two different isoantisera revealed a group of proteins with a molecular weight ofM, 65‐70,000 present in both clones. Furthermore, immunoprecipitation with the A7‐1 mAb again showed a singleM, 65K band present in A7 and B9 clones. We conclude that the marked differences observed in the syngeneic growth of the two clones are not due to differences in tumour associated antigens (TAA), defined by syngeneic antibodies, and emphasize the role that class I H‐2 antigens could pla

ISSN:1744-3121    

DOI:10.1111/j.1744-313X.1986.tb01098.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYThe correlation between gene expression and DNA methylation is well established. In the present study we examined DNA methylation as a potential regulatory mechanism of class I histocompatibility antigen expression. We selected for study two cell clones from the same mouse tumour (GR9). One of them is H‐2 class I‐positive (A7) and the other negative (B9). Using five enzymes and three different probes, no rearrangement or deletion was detected in the MHC class I genes of the negative clone compared with the positive one. These results do not provide an explanation for the differences observed in the expression of class I antigens in A7 (Kd, Ddpositive) and B9 (Kd, Ddnegative). We then studied the DNA methylation status in both clones by Southern blot analysis. Clear differences between the Kd, Ddpositive and negative clones were detected. Furthermore, both Kdand Ddwere clearly expressed after culturing the H‐2 class I negative clone with the demethylating agent 5‐azacytidine. These results suggest that the methylation of certain MHC cytoshes is a regulatory mechanism of H‐2 class I gene e

ISSN:1744-3121    

DOI:10.1111/j.1744-313X.1986.tb01099.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYWe have analysed the factors which regulate MHC class II expression in mouse T cell lines. Two such lines, BW 5147 and PLT‐24.2, were used in this study. Using 5‐azacytidine (5 AzaC) we have shown that hypomethylation of DNA can induce class II antigen synthesis in BW 5147. The expression of class II in PLT‐24.2 cells seems to be under a different control mechanism. Southern blot analysis of I‐Aβ gene in PLT‐24.2 suggests that the expression of class II in this cell line is probably the outcome of a gene rearrangement. We hypothesise that insertion of viral long terminal repeats (LTR) next to the class II genes in transformed T cell lines can act as a promoter for the expression of class I

ISSN:1744-3121    

DOI:10.1111/j.1744-313X.1986.tb01100.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYBy means of immunoperoxidase staining of frozen sections 100 primary colorectal carcinomas and 19 metastases were studied for the expression of HLA‐A,B,C antigens. A substantial number of the tumours showed a deficient class I expression. The loss of HLA‐A,B,C correlated with the degree of de‐differenti

ISSN:1744-3121    

DOI:10.1111/j.1744-313X.1986.tb01101.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYThe MHC status of epithelial cells from 32 primary colorectal neoplasms, villous adenomata (VA; 2) and inflammatory bowel disease (IBD; 3) were evaluated using a panel of monoclonal antibodies (mAbs). Class I antigens and β2microglobulin (β2m) were expressed on all normal, benign, inflammatory and malignant epithelia with the exception of two carcinomas. A more complex pattern of reactivity was encountered with anti‐class II mAbs. Some expression was detected on normal glandular and luminal epithelium, particularly adjacent to the tumour. Inflammatory tissues, VA and 23/32 carcinomas were also antigen‐positive, the proportion of stained epithelial cells ranging from 5% to 90%. Expression was usually non‐coordinate, DR being the predominant specificity followed by DP and DQ, which is suggestive of independentDregion gene regulation. The hypothesis that class II expression is inducedin vivoby locally generated IFN γ was not confirmed byin vitrotreatment with this agent of epithelial colorectal carcinoma‐derived cell lines. These provisional data suggest that although IFN γ may be a necessary stimulus for class II expression it is insufficient and that other factors also influence the responsiveness of tumour cells in t

ISSN:1744-3121    

DOI:10.1111/j.1744-313X.1986.tb01102.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYIt has been recently established that there is a correlation between the lack of MHC class I gene expression on murine tumour cells and their ability to grow and metastasize. We have studied the expression of HLA‐ABC and HLA‐DR products on human malignant tumours from the digestive tract using monoclonal antibodies, by indirect immunofluorescence on the cell suspensions obtained from 29 freshly explanted digestive tumours. Our results show that digestive tract cancers have an heterogeneous expression of HLA class I molecules on their surface. Whereas 50% have high levels of expression of these molecules (more than 60% positive cells), 25% have a moderate level of expression (20‐60% positive cells) and 25% have weak expression (less than 20% positive cells).It has been found that there is a correlation between the level of HLA class I molecule expression and the degree of histological differentiation of a tumour. The absence of MHC class I antigens on human tumour cells, detected in this study, may play a relevant role in oncogenesis, as has been established in experimental m

ISSN:1744-3121    

DOI:10.1111/j.1744-313X.1986.tb01103.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY