M. Nicolis - Academia.edu (original) (raw)

Papers by M. Nicolis

Research paper thumbnail of Interspecies somatic T cell hybrids as biological tools for studying gene expression during T cell development

International journal of clinical & laboratory research, 1994

Interspecies somatic cell hybrids were generated by fusing the mouse thymic lymphoma cell line, B... more Interspecies somatic cell hybrids were generated by fusing the mouse thymic lymphoma cell line, BW5147, with normal human T lymphocytes at different stages of differentiation. Thymocytes, activated peripheral T lymphocytes, or an activated T cell clone were used as human partners, respectively, in three independent fusions. Phenotype and genetic analysis demonstrated that these hybrids preferentially segregated human chromosomes while retaining a complete mouse genetic complement, irrespective of the human partner used for fusion. A large number of T cell differentiation antigens constitutively expressed throughout the T lymphocyte development remained constitutively expressed in the hybrids, irrespective of the maturation stage of human partner used for fusion. In contrast, the expression of other antigens related to a specific stage of T cell development (CD2, CD8), or to an activated state of T lymphocytes (HLA-DR, CD25), was to observed in the hybrids, with no apparent correlati...

Research paper thumbnail of Evidence for a specific post-transcriptional mechanism controlling the expression of HLA-DQ, but not -DR and -DP, molecules

Journal of immunology (Baltimore, Md. : 1950), Jan 15, 1994

It is generally believed that the various MHC class II molecules are expressed coordinately in B ... more It is generally believed that the various MHC class II molecules are expressed coordinately in B cells. To investigate this aspect in more detail, interspecies somatic cell hybrids were constructed between Raji or RJ 2.2.5 (a class II-negative derivative of Raji) human B cells and M12.4.1 mouse B cells. In both types of hybrids, HLA-DR and -DP, but not -DQ, molecules were expressed at the cell surface. The specific lack of expression of DQ Ags correlated with undetectability of newly synthesized DQ alpha beta heterodimers, as assessed by biosynthetic labeling and immunoprecipitation with a variety of DQ-specific mAbs. Studies at the mRNA level showed that apparently normal DQ alpha and DQ beta transcripts were present in the hybrids at levels comparable, if not higher, with the levels of DR- and DP-specific transcripts. From these results, we conclude that lack of appreciable amount of DQ molecules in the hybrids is caused by a post-transcriptional block. To date, these findings rep...

Research paper thumbnail of Expression of MHC class I and class II antigens in pancreatic adenocarcinomas

Tissue Antigens

The antigens encoded by the major histocompatibility complex (MHC) are cell surface glycoproteins... more The antigens encoded by the major histocompatibility complex (MHC) are cell surface glycoproteins that play a fundamental role in the regulation of the immune response. Anomalous MHC expression in tumor cells has been viewed as an important feature to escape tumor recognition by immune cells. Low or absent MHC class I expression as well as ectopic MHC class II expression have been often observed to correlate with high grade malignancy and metastatic potential in a variety of human cancers. To date, very little investigation of MHC (HLA in man) class I and class II expression in human pancreatic cancer has been reported. We investigated this aspect on frozen sections of 8 pancreatic adenocarcinomas and 18 established in vitro cell lines. HLA class I was expressed in all but two cancers whereas de novo HLA class II expression was detected in 3 of 8 cancers. Interestingly, a hierarchy in the expression of the various subsets of HLA class II was found with HLA- DR > -DP > -DQ. Res...

Research paper thumbnail of Respiratory Symptoms, Asthma, Atopy and Chlamydia pneumoniae IgG Antibodies in a General Population Sample of Young Adults

Infection, 2002

Background: This study was designed to test the association of Chlamydia pneumoniae infection wit... more Background: This study was designed to test the association of Chlamydia pneumoniae infection with respiratory symptoms and atopy. Methods: A general population sample of 369 young adults (aged 20-44 years) completed a questionnaire on respiratory symptoms and underwent skin prick testing. C. pneumoniae IgG and IgM serum titers were measured by microimmunofluorescence. Prior infection was defined by titers of IgG ≥ 1:32, acute infection by titers of IgG ≥ 1:512 and/or IgM ≥ 1:16. Results: The prevalence of cough and phlegm was higher in subjects with (19.0%) than in those without (11.4%) prior C. pneumoniae infection (p = 0.01). A similar difference was found for wheezing (14.3% vs 8.0%; p = 0.05), whereas the percentage of asthmatics was equally distributed between seropositive and seronegative subjects. IgG titers ≥ 1:128 were found more frequently in atopic subjects (p = 0.04). After adjusting for any confounding factors, cough and phlegm (but not wheezing) were found significantly associated with C. pneumoniae positivity, both for 1 : 32 (OR 1.80; 95% CI: 1.01-3.36; p = 0.05) and for 1 : 128 titers (OR 2.31; 95% CI: 1.20-4.42; p = 0.01). A significant association was also found for atopy, for titers ≥ 1 : 128 (OR 1.73; 95% CI: 1.01-3.20, p = 0.05). Acute infection was not associated with respiratory symptoms or asthma. Conclusion: We conclude that C. pneumoniae infection is associated with cough and phlegm and may have a role in the pathogenesis of chronic respiratory diseases. Moreover, our results indicate a relationship between atopy and C. pneumoniae infection.

Research paper thumbnail of Induction of CIITA and modification of in vivo HLA-DR promoter occupancy in normal thymic epithelial cells treated with IFN-gamma: similarities and distinctions with respect to HLA-DR-constitutive B cells

In this study, the IFN-gamma induction of MHC class II gene expression in primary cultures of thy... more In this study, the IFN-gamma induction of MHC class II gene expression in primary cultures of thymic epithelial cells (TEC) was analyzed. This cellular system offers the advantage that MHC class II induction is studied in a "physiologic" cell lineage that, as a result of this expression within the thymus, is thought to participate to the selection and maturation of the T cells. It was found that the MHC class II gene expression was associated with the de novo transcription of the gene encoding the CIITA trans-activator, a crucial MHC class II gene regulatory factor. Furthermore, the anatomy of interaction between the MHC class II DRA promoter and corresponding binding factors was analyzed by in vivo DNAse I footprint. It was found that treatment with IFN-gamma induces changes in the occupancy of the DRA gene regulatory sequences by nuclear factors. The resulting occupancy displays strong similarities with the one observed in the MHC class II-constitutive B cells, represented by both the Burkitt lymphoma line Raji and normal tonsil- derived B cells. However, some peculiar differences were observed between the TEC, either IFN-gamma-induced or not, and the constitutive B cells. These results suggest that both common mechanisms, such as the one mediated by the CIITA trans-activator, and distinct tissue-specific constraints contribute to the transcriptional control of constitutive and IFN-gamma-induced MHC class II gene expression.

Research paper thumbnail of Divergent evolution in the mechanisms controlling major histocompatibility complex class II gene transcription in mouse and human

European Journal of Immunology, 1996

The expression of the major histocompatibility complex (MHC) class I1 gene family is developmenta... more The expression of the major histocompatibility complex (MHC) class I1 gene family is developmentally regulated and, in general, in a coordinate manner. In this study, we show that the expression of the entire repertoire of human class I1 genes, otherwise transcriptionally silent in the bare lymphocyte syndromederived BLSl cell line, can be rescued by somatic cell hybridization with normal mouse spleen cells. The analysis of the interspecies cell hybrids revealed a particularly important and unprecedented aspect. A return to the BLS1-like, human M H C class 11-negative phenotype due to segregation of mouse chromosomes was accompanied in certain hybrids by loss of IE, but not I A cell surface antigen expression. At the molecular level, this was the result of lack of Ea-specific mRNA in the presence of EP-, A a -and AB-specific mRNA. Thus, the mouse truns-acting function operating across species barriers and able to complement the defect of human BLSl cells diverged in mice to control E a , but not Eb, A a and A b gene expression. These findings suggest that evolutionary pressure has maintained the expression of the M H C class 11 multigene family under the control of quite distinct species-specific transcriptional mechanisms.

Research paper thumbnail of Interspecies somatic T cell hybrids as biological tools for studying gene expression during T cell development

International journal of clinical & laboratory research, 1994

Interspecies somatic cell hybrids were generated by fusing the mouse thymic lymphoma cell line, B... more Interspecies somatic cell hybrids were generated by fusing the mouse thymic lymphoma cell line, BW5147, with normal human T lymphocytes at different stages of differentiation. Thymocytes, activated peripheral T lymphocytes, or an activated T cell clone were used as human partners, respectively, in three independent fusions. Phenotype and genetic analysis demonstrated that these hybrids preferentially segregated human chromosomes while retaining a complete mouse genetic complement, irrespective of the human partner used for fusion. A large number of T cell differentiation antigens constitutively expressed throughout the T lymphocyte development remained constitutively expressed in the hybrids, irrespective of the maturation stage of human partner used for fusion. In contrast, the expression of other antigens related to a specific stage of T cell development (CD2, CD8), or to an activated state of T lymphocytes (HLA-DR, CD25), was to observed in the hybrids, with no apparent correlati...

Research paper thumbnail of Evidence for a specific post-transcriptional mechanism controlling the expression of HLA-DQ, but not -DR and -DP, molecules

Journal of immunology (Baltimore, Md. : 1950), Jan 15, 1994

It is generally believed that the various MHC class II molecules are expressed coordinately in B ... more It is generally believed that the various MHC class II molecules are expressed coordinately in B cells. To investigate this aspect in more detail, interspecies somatic cell hybrids were constructed between Raji or RJ 2.2.5 (a class II-negative derivative of Raji) human B cells and M12.4.1 mouse B cells. In both types of hybrids, HLA-DR and -DP, but not -DQ, molecules were expressed at the cell surface. The specific lack of expression of DQ Ags correlated with undetectability of newly synthesized DQ alpha beta heterodimers, as assessed by biosynthetic labeling and immunoprecipitation with a variety of DQ-specific mAbs. Studies at the mRNA level showed that apparently normal DQ alpha and DQ beta transcripts were present in the hybrids at levels comparable, if not higher, with the levels of DR- and DP-specific transcripts. From these results, we conclude that lack of appreciable amount of DQ molecules in the hybrids is caused by a post-transcriptional block. To date, these findings rep...

Research paper thumbnail of Expression of MHC class I and class II antigens in pancreatic adenocarcinomas

Tissue Antigens

The antigens encoded by the major histocompatibility complex (MHC) are cell surface glycoproteins... more The antigens encoded by the major histocompatibility complex (MHC) are cell surface glycoproteins that play a fundamental role in the regulation of the immune response. Anomalous MHC expression in tumor cells has been viewed as an important feature to escape tumor recognition by immune cells. Low or absent MHC class I expression as well as ectopic MHC class II expression have been often observed to correlate with high grade malignancy and metastatic potential in a variety of human cancers. To date, very little investigation of MHC (HLA in man) class I and class II expression in human pancreatic cancer has been reported. We investigated this aspect on frozen sections of 8 pancreatic adenocarcinomas and 18 established in vitro cell lines. HLA class I was expressed in all but two cancers whereas de novo HLA class II expression was detected in 3 of 8 cancers. Interestingly, a hierarchy in the expression of the various subsets of HLA class II was found with HLA- DR > -DP > -DQ. Res...

Research paper thumbnail of Respiratory Symptoms, Asthma, Atopy and Chlamydia pneumoniae IgG Antibodies in a General Population Sample of Young Adults

Infection, 2002

Background: This study was designed to test the association of Chlamydia pneumoniae infection wit... more Background: This study was designed to test the association of Chlamydia pneumoniae infection with respiratory symptoms and atopy. Methods: A general population sample of 369 young adults (aged 20-44 years) completed a questionnaire on respiratory symptoms and underwent skin prick testing. C. pneumoniae IgG and IgM serum titers were measured by microimmunofluorescence. Prior infection was defined by titers of IgG ≥ 1:32, acute infection by titers of IgG ≥ 1:512 and/or IgM ≥ 1:16. Results: The prevalence of cough and phlegm was higher in subjects with (19.0%) than in those without (11.4%) prior C. pneumoniae infection (p = 0.01). A similar difference was found for wheezing (14.3% vs 8.0%; p = 0.05), whereas the percentage of asthmatics was equally distributed between seropositive and seronegative subjects. IgG titers ≥ 1:128 were found more frequently in atopic subjects (p = 0.04). After adjusting for any confounding factors, cough and phlegm (but not wheezing) were found significantly associated with C. pneumoniae positivity, both for 1 : 32 (OR 1.80; 95% CI: 1.01-3.36; p = 0.05) and for 1 : 128 titers (OR 2.31; 95% CI: 1.20-4.42; p = 0.01). A significant association was also found for atopy, for titers ≥ 1 : 128 (OR 1.73; 95% CI: 1.01-3.20, p = 0.05). Acute infection was not associated with respiratory symptoms or asthma. Conclusion: We conclude that C. pneumoniae infection is associated with cough and phlegm and may have a role in the pathogenesis of chronic respiratory diseases. Moreover, our results indicate a relationship between atopy and C. pneumoniae infection.

Research paper thumbnail of Induction of CIITA and modification of in vivo HLA-DR promoter occupancy in normal thymic epithelial cells treated with IFN-gamma: similarities and distinctions with respect to HLA-DR-constitutive B cells

In this study, the IFN-gamma induction of MHC class II gene expression in primary cultures of thy... more In this study, the IFN-gamma induction of MHC class II gene expression in primary cultures of thymic epithelial cells (TEC) was analyzed. This cellular system offers the advantage that MHC class II induction is studied in a "physiologic" cell lineage that, as a result of this expression within the thymus, is thought to participate to the selection and maturation of the T cells. It was found that the MHC class II gene expression was associated with the de novo transcription of the gene encoding the CIITA trans-activator, a crucial MHC class II gene regulatory factor. Furthermore, the anatomy of interaction between the MHC class II DRA promoter and corresponding binding factors was analyzed by in vivo DNAse I footprint. It was found that treatment with IFN-gamma induces changes in the occupancy of the DRA gene regulatory sequences by nuclear factors. The resulting occupancy displays strong similarities with the one observed in the MHC class II-constitutive B cells, represented by both the Burkitt lymphoma line Raji and normal tonsil- derived B cells. However, some peculiar differences were observed between the TEC, either IFN-gamma-induced or not, and the constitutive B cells. These results suggest that both common mechanisms, such as the one mediated by the CIITA trans-activator, and distinct tissue-specific constraints contribute to the transcriptional control of constitutive and IFN-gamma-induced MHC class II gene expression.

Research paper thumbnail of Divergent evolution in the mechanisms controlling major histocompatibility complex class II gene transcription in mouse and human

European Journal of Immunology, 1996

The expression of the major histocompatibility complex (MHC) class I1 gene family is developmenta... more The expression of the major histocompatibility complex (MHC) class I1 gene family is developmentally regulated and, in general, in a coordinate manner. In this study, we show that the expression of the entire repertoire of human class I1 genes, otherwise transcriptionally silent in the bare lymphocyte syndromederived BLSl cell line, can be rescued by somatic cell hybridization with normal mouse spleen cells. The analysis of the interspecies cell hybrids revealed a particularly important and unprecedented aspect. A return to the BLS1-like, human M H C class 11-negative phenotype due to segregation of mouse chromosomes was accompanied in certain hybrids by loss of IE, but not I A cell surface antigen expression. At the molecular level, this was the result of lack of Ea-specific mRNA in the presence of EP-, A a -and AB-specific mRNA. Thus, the mouse truns-acting function operating across species barriers and able to complement the defect of human BLSl cells diverged in mice to control E a , but not Eb, A a and A b gene expression. These findings suggest that evolutionary pressure has maintained the expression of the M H C class 11 multigene family under the control of quite distinct species-specific transcriptional mechanisms.