Characterization of mature and immature Rad LV-Induced thymic T-cell lines for tumorigenesis and mhc-class-I gene expression

1995 ◽  
Vol 61 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Orna Bashi ◽  
Rachel Ehrlich
Blood ◽  
1991 ◽  
Vol 78 (2) ◽  
pp. 524-532 ◽  
Author(s):  
RA Zeff ◽  
YF Zhao ◽  
R Tatake ◽  
H Lachman ◽  
F Borriello ◽  
...  

Abstract Numerous tumor cell lines of leukemic origin are known to modulate cell surface expression of major histocompatibility complex (MHC) class I antigens resulting in alterations in their immune detection and tumorigenicity. We have been studying the mechanisms responsible for attenuation of MHC class I gene expression in an H-2 heterozygous (H-2b x H-2d) Abelson-Murine leukemia virus (A-MuLV)-transformed leukemic cell line (designated R8). Here we report that treatment of the R8 cell line with the protein synthesis inhibitor cycloheximide (CHX) increased H-2Kb steady-state messenger RNA (mRNA) levels several fold. The induced H-2Kb mRNA transcripts were functional, as demonstrated by their ability to be translated into immunoprecipitable H-2Kb alloantigen. H-2Kb null variants derived from the R8 cell line were shown to be the product of both cis- and trans-acting mechanisms, insomuch as the treatment of R8-derived H-2Kb non-expressor lines with CHX re-established expression of H-2Kb mRNA to the same extent as transfection of the variant cell line with the wild-type H-2Kb gene. Such findings indicate that downregulation of MHC class I gene expression is constitutive for the R8 leukemic cell line, a phenomenon that may be related to the immature pre-B-cell phenotype of this A-MuLV transformant.


2006 ◽  
Vol 189 (3) ◽  
pp. 605-615 ◽  
Author(s):  
C Giuliani ◽  
M Saji ◽  
I Bucci ◽  
G Fiore ◽  
M Liberatore ◽  
...  

Increased major histocompatibility complex (MHC) class I gene expression in nonimmune cell ‘target tissues’ involved in organ-specific diseases may be important in the pathogenesis of autoimmune diseases. This possibility in part evolves from studies of cultured thyrocytes where properties appear relevant to the development of thyroid autoimmune disease. In FRTL-5 rat thyroid cells in continuous culture, hormones and growth factors that regulate cell growth and function specifically decrease MHC class I gene expression. We hypothesized that this could reflect a mechanism to preserve self-tolerance and prevent autoimmune disease. The mechanisms of action of some of these hormones, namely TSH and hydrocortisone, have been already characterized. In this report, we show that IGF-I transcriptionally downregulates MHC class I gene expression and that its action is similar to that of insulin. The two hormones have a complex effect on the promoter of the MHC class I gene, PD1. In fact, they decrease the full promoter activity, but upregulate the activity of deleted mutants that have lost an upstream, tissue-specific regulatory region but still retain the enhancer A region. We show that insulin/IGF-I promotes the interactions of the p50/p65 subunits of NF-κB and AP-1 family members with these two regions, and that the tissue-specific region acts as a dominant silencer element on insulin/IGF-I regulation of promoter activity. These observations may be important to understand how MHC class I gene transcription is regulated in the cells.


2013 ◽  
Vol 20 (3) ◽  
pp. 328-340 ◽  
Author(s):  
Riva Kovjazin ◽  
David Shitrit ◽  
Rachel Preiss ◽  
Ilanit Haim ◽  
Lev Triezer ◽  
...  

ABSTRACTThe low protection by the bacillus Calmette-Guérin (BCG) vaccine and existence of drug-resistant strains require better anti-Mycobacterium tuberculosisvaccines with a broad, long-lasting, antigen-specific response. Using bioinformatics tools, we identified five 19- to 40-mer signal peptide (SP) domain vaccine candidates (VCs) derived fromM. tuberculosisantigens. All VCs were predicted to have promiscuous binding to major histocompatibility complex (MHC) class I and II alleles in large geographic territories worldwide. Peripheral mononuclear cells (PBMC) from healthy naïve donors and tuberculosis patients exhibited strong proliferation that correlated positively with Th1 cytokine secretion only in healthy naïve donors. Proliferation to SP VCs was superior to that to antigen-matched control peptides with similar length and various MHC class I and II binding properties. T-cell lines induced to SP VCs from healthy naïve donors had increased CD44high/CD62L+activation/effector memory markers and gamma interferon (IFN-γ), but not interleukin-4 (IL-4), production in both CD4+and CD8+T-cell subpopulations. T-cell lines from healthy naïve donors and tuberculosis patients also manifested strong, dose-dependent, antigen-specific cytotoxicity against autologous VC-loaded orM. tuberculosis-infected macrophages. Lysis ofM. tuberculosis-infected targets was accompanied by high IFN-γ secretion. Various combinations of these five VCs manifested synergic proliferation of PBMC from selected healthy naïve donors. Immunogenicity of the best three combinations, termed Mix1, Mix2, and Mix3 and consisting of 2 to 5 of the VCs, was then evaluated in mice. Each mixture manifested strong cytotoxicity againstM. tuberculosis-infected macrophages, while Mix3 also manifested a VC-specific humoral immune response. Based on these results, we plan to evaluate the protection properties of these combinations as an improved tuberculosis subunit vaccine.


BioFactors ◽  
2016 ◽  
Vol 42 (4) ◽  
pp. 349-357 ◽  
Author(s):  
Isaac Downs ◽  
Saptha Vijayan ◽  
Tabasum Sidiq ◽  
Koichi S. Kobayashi

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