Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A key aspect of the immune response to adenovirus (Ad) gene therapy is the generation of a cytotoxic T-cell (CTL) response. To better understand the genetic network underlying these events, 20 strains of C57BL/6 x DBA/2 (BXD) recombinant inbred (RI) mice were administered with AdLacZ and analyzed at days 7, 21, 30, and 50 for liver beta-galactosidase (LacZ) expression and CTL response. Sera levels of interferon gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were analyzed at different times after AdLacZ. There was a distinct strain-dependent expression of LacZ, which was strongly correlated with the CTL response. Among the five BXD RI strains that exhibited significantly prolonged LacZ expression, four also exhibited a marked defect in the production of Ad-specific CTL. There was a strong correlation between the sera levels of IFN-gamma, TNF-alpha, and IL-6, but cytokine responses were not significantly correlated with LacZ expression or the CTL response. Quantitative trait loci regulating LacZ on day 30 were found on chromosome (Chr) 19 (33 cM) and Chr 15 (42.8 cM). Cytotoxicity mapped to Chr 7 (41.0 and 57.4-65.2 cM), Chr 15 (61.7 cM), and Chr X (27.8 cM). IFN-gamma production mapped to Chr 18 (22, 27, and 32 cM) and Chr 11 (64.0 cM). TNF-alpha and IL-6 production mapped to Chr 6 (91.5 cM) Chr 9 (42.0 cM) and Chr 8 (52 and 73.0 cM). These results indicate that different strains of mice exhibit different pathways for effective clearance of AdLacZ depending on genetic polymorphisms and interactions at multiple genetic loci.
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PMID:Identification of multiple genetic loci that regulate adenovirus gene therapy. 1468 91

This study describes a tumor vaccine-induced secondary in vivo T cell response to an immunodominant epitope of beta-galactosidase (Gal) as a model tumor-associated antigen. DBA/2 mice are primed with lacZ transfected live ESbL tumor cells (ESbL-Gal) in the ear pinna, a site which had previously been shown to be non-tumorigenic and immunogenic. Intraperitoneal challenge of such mice with tumor vaccine (i.e., 10(7) irradiation-inactivated ESbL-Gal cells) leads to the production of a powerful CD8+ CTL response and to the establishment of immune memory. Using peptide/MHC-tetrameric complexes, clonal expansion of antigen-specific T cells could be detected during the primary response in bone marrow (BM) and during the secondary response in the peritoneal cavity and BM. The secondary response in the peritoneal cavity involved a >80-fold enrichment of epitope specific CD8+ T cells and the release of various cytokines, including IL-12 and TNF-alpha. The recruitment and/or expansion of Gal specific T cells within the peritoneal cavity could be inhibited by anti-IL-12 and anti-TNF-alpha monoclonal antibody (mAb) treatment. Interestingly, the secondary CTL response was inhibited by anti-IL-12 but not by anti-TNF-alpha mAb. The results characterize a strong systemic CD8+ memory T cell response to a cell bound antigen without the use of adjuvant.
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PMID:Characteristics of a potent tumor vaccine-induced secondary anti-tumor T cell response. 1513 84

Data on the duration of transgene expression in the liver, the presence of cytotoxic T lymphocytes (CTLs) against adenovirus, and serum cytokines from 18 strains of C57BL/6 x DBA/2 (B x D) recombinant inbred mice were analyzed. Our aim was to detect quantitative trait loci (QTLs) that may have causal relationship with the duration of adenovirus-mediated transgene expression in the liver. Information from beta-galactosidase (LacZ) expression; CTL production; and serum levels of gamma interferon, tumor necrosis factor-alpha, and interleukin-6 30 days after intravenous injection of liver LacZ were summarized by principal component analysis and analyzed using maximum likelihood interval mapping implemented in the QTL cartographer software. Two principal component (PC) scores explained 82.5% of the phenotypic variance in the original variables and identified QTLs not identified by analysis of individual traits. The distribution of original variables among PCs was such that variables in PC1 were predominantly cytokines with little CTL response whereas LacZ and CTL were the predominant contributors to PC2 with practically no contribution from cytokines. PC1 was significantly associated with two QTLs on chromosomes 7 and 9 located at 57.5 cM and 41.01 cM, respectively. Five QTLs were significantly associated with PC2 on chromosomes 12 (23.01 and 31.01 cM) and 15 (29.21, 36.01, and 56.31 cM). These results illustrate the use of principal component analysis in mapping QTLs using multiple correlated traits.
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PMID:Principal component analysis of quantitative trait loci for immune response to adenovirus in mice. 1736 54


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