To lay background for studying rejection mechanisms in xenotransplantation and developing the strategies for intervention, class I genes of swine leukocyte antigens (SLA) of three Chinese pig strains Bm, Gz and Yn wer...To lay background for studying rejection mechanisms in xenotransplantation and developing the strategies for intervention, class I genes of swine leukocyte antigens (SLA) of three Chinese pig strains Bm, Gz and Yn were cloned and sequenced. The cDNA of the class I loci P1 and P14 were amplified by RT-PCR and subjected to insert into sequencing vectors. All six allelic sequences we examined, each two for one Chinese strain, are not identical to those reported, which allows these novel sequences receiving their accession numbers AY102467- AY102472 from GenBank. This study further reveals that the homologies of MHC class I genes in their primary structures and the deduced amino acids between Chinese pigs (SLA) and human (HLA-A*0201) are better than those between pigs and mice (H-2Db/H-2Kb). The comparison also indicates that the amino acid residues critical for recognition by human KIRs are altered in the swine class I molecules. The amino acids responsible for binding human CD8 coreceptor are largely conserved although there are two critical residues substituted. A functional test indicated that the human T cells specific for the prokaryotically expressed SLA Plprotein could respond quite well in vitro to the class I-positive swine chon-drocytes and PBMCs in presence of human APCs. This implies that, due to the substitution of two critical residues, the inaccessibility of human CD8 coreceptor to swine class I molecule might be contributable to the indirect pathway that the human T cells have to use for recognizing the SLA class I xenogeneic antigens.展开更多
The chemokine receptors CCR5 and CXCR4 play an important role as coreceptors for human immunodeficiency virus type 1 （HIV-1） entring into cells. HIV-1 isolates can be distinguished by the chemokine coreceptors. Nons...The chemokine receptors CCR5 and CXCR4 play an important role as coreceptors for human immunodeficiency virus type 1 （HIV-1） entring into cells. HIV-1 isolates can be distinguished by the chemokine coreceptors. Nonsyncytium inducing （NSI）, macrophage tropic viruses utilizing CCR5, are called R5 viruses; syncytium inducing （SI） isolates use CXCR4 and known as X4 viruses. R5 viruses generally are associated with latent stage of infection and X4 viruses with later,展开更多
To elucidate the structures of SLA-DR(swine leukocyte antigen DR)genes of three Chinese pig strains (Gz,Bm and Yn),the SLA-DRA and SLA-DRB cDNA were amplified by RT-PCR and subjected to determine the sequences.The who...To elucidate the structures of SLA-DR(swine leukocyte antigen DR)genes of three Chinese pig strains (Gz,Bm and Yn),the SLA-DRA and SLA-DRB cDNA were amplified by RT-PCR and subjected to determine the sequences.The whole structures of SLA-DRA alleles are identical among three strains,consisting of 759 nucleotides including an open reading frame(ORF),and are shared with those reported from NIH minipigs SLA-DRA^c and SLA-DRA^d.The same length of the ORF-containing SLA-DRB genes of three Chinese pig strains was also identified.They are composed of 801 nucleotides encoding a xenogeneic antigen molecule of 266 amino acid residues.The nucleotide sequences of the SLA-DRB genes,however,are different when compared either among the three strains or with the published data of SLA-DRB sequences,which allowed our novel SLA-DRB alleles receiving their accession numbers AY102479,AY102480 and AY102481 from the GenBank.This study further reveals that the phylogenic homologies of MHC DR or DR-like genes in structures of nucleotides and deduced amino acids between Chinese pigs(SLA)and human(HLA-DRB1*0901)are better than those between pigs and mice (H-2~b Eβ).High similarities were also found for DRα-DRβ heterodimers between Chinese pigs and human in terms of amino acids sequences critical for binding with human CD4 coreceptor molecule,which are better than those between SLA-DR and H-2 I-E molecules.A functional test indicated that,by cotransfection with Bm-DRA and Bm-DRB genes,the Bm-DR molecule-expressed L929 cells could stimulate human T cells quite well in a xenogeneic reaction in presence of human APCs.Cellular & Molecular Immunology.2004;1 (3):212-218.展开更多
Epstein-Barr virus(EBV)-associated gastric cancer(EBVaGC)cells originate from a single-cell clone infected with EBV.However,more than 95%of patients with gastric cancer have a history of Helicobacter pylori(H.pylori)i...Epstein-Barr virus(EBV)-associated gastric cancer(EBVaGC)cells originate from a single-cell clone infected with EBV.However,more than 95%of patients with gastric cancer have a history of Helicobacter pylori(H.pylori)infection,and H.pylori is a major causative agent of gastric cancer.Therefore,it has long been argued that H.pylori infection may affect the development of EBVaGC,a subtype of gastric cancer.Atrophic gastrointestinal inflammation,a symptom of H.pylori infection,is observed in the gastric mucosa of EBVaGC.Therefore,it remains unclear whether H.pylori infection is a cofactor for gastric carcinogenesis caused by EBV infection or whether H.pylori and EBV infections act independently on gastric cancer formation.It has been reported that EBV infection assists in the oncogenesis of gastric cancer caused by H.pylori infection.In contrast,several studies have reported that H.pylori infection accelerates tumorigenesis initiated by EBV infection.By reviewing both clinical epidemiological and experimental data,we reorganized the role of H.pylori and EBV infections in gastric cancer formation.展开更多
Objective Although HIV-1 infection is prevalent in many regions in China, it remains largely unknown on the biological characteristics of dominant circulating isolates. This study was designed to isolate the circulati...Objective Although HIV-1 infection is prevalent in many regions in China, it remains largely unknown on the biological characteristics of dominant circulating isolates. This study was designed to isolate the circulating viral strains from different prevalent regions and to characterize their biological properties and neutralization sensitivity. Methods Primary viruses were isolated from fresh PBMCs using the traditional co-culture method and their capacity of inducing syncytium was tested in MT-2 cells. Meanwhile, their coreceptor usage was determined with two cell lines: Magi and GHOST (3) stably expressing CD4 and the chemokine receptor CCR5 or CXCR4. Furthermore, the sensitivity of these viruses to neutralization by HIV-1-infected patients’ plasma which were highly active to neutralize SF33 strain, was quantified in GHOST cell-based neutralization assay. Results Six primary viral strains were isolated from 4 separated regions. Isolates LTG0213,LTG0214 and XVS032691 induced syncytia in MT-2 cells, and used CXCR4 as coreceptor. Isolates XJN0021, XJN0091, or SHXDC0041 did not induce syncytia, and used CCR5 as coreceptor. Overall neutralization sensitivity differed among four representative strains: HIV-1 XVS032691>LTG0214>XJN0091≈SHXDC0041. Conclusion The neutralization sensitivity of HIV isolates is linked with the phenotype of isolates, in which syncytium-inducing (SI) or CXCR4-tropic (X4) viruses are more easily neutralized than non-syncytium-inducing (NSI) or CCR5-tropic (R5) viruses. The genetic subtypes based on the phylogeny of env sequences are not classical neutralization serotypes.展开更多
基金supported by the grants from National Natural Science Foundation of China(No.39993430-2,30000157)
文摘To lay background for studying rejection mechanisms in xenotransplantation and developing the strategies for intervention, class I genes of swine leukocyte antigens (SLA) of three Chinese pig strains Bm, Gz and Yn were cloned and sequenced. The cDNA of the class I loci P1 and P14 were amplified by RT-PCR and subjected to insert into sequencing vectors. All six allelic sequences we examined, each two for one Chinese strain, are not identical to those reported, which allows these novel sequences receiving their accession numbers AY102467- AY102472 from GenBank. This study further reveals that the homologies of MHC class I genes in their primary structures and the deduced amino acids between Chinese pigs (SLA) and human (HLA-A*0201) are better than those between pigs and mice (H-2Db/H-2Kb). The comparison also indicates that the amino acid residues critical for recognition by human KIRs are altered in the swine class I molecules. The amino acids responsible for binding human CD8 coreceptor are largely conserved although there are two critical residues substituted. A functional test indicated that the human T cells specific for the prokaryotically expressed SLA Plprotein could respond quite well in vitro to the class I-positive swine chon-drocytes and PBMCs in presence of human APCs. This implies that, due to the substitution of two critical residues, the inaccessibility of human CD8 coreceptor to swine class I molecule might be contributable to the indirect pathway that the human T cells have to use for recognizing the SLA class I xenogeneic antigens.
基金This study was supported by the grants from the Ministry of Science and Technology of People's Republic of China(No.2005CB523103 and No.2005CB522903)the US NIH grants(No.U19AIS1915-03)
文摘The chemokine receptors CCR5 and CXCR4 play an important role as coreceptors for human immunodeficiency virus type 1 （HIV-1） entring into cells. HIV-1 isolates can be distinguished by the chemokine coreceptors. Nonsyncytium inducing （NSI）, macrophage tropic viruses utilizing CCR5, are called R5 viruses; syncytium inducing （SI） isolates use CXCR4 and known as X4 viruses. R5 viruses generally are associated with latent stage of infection and X4 viruses with later,
基金supported by the grants from the National Natural Science Foundation of China(39993430-2)the National 863 Foundation(2003AA205009)the Foundation of Shanghai Sci-Tech Committee(04JC14085).
文摘To elucidate the structures of SLA-DR(swine leukocyte antigen DR)genes of three Chinese pig strains (Gz,Bm and Yn),the SLA-DRA and SLA-DRB cDNA were amplified by RT-PCR and subjected to determine the sequences.The whole structures of SLA-DRA alleles are identical among three strains,consisting of 759 nucleotides including an open reading frame(ORF),and are shared with those reported from NIH minipigs SLA-DRA^c and SLA-DRA^d.The same length of the ORF-containing SLA-DRB genes of three Chinese pig strains was also identified.They are composed of 801 nucleotides encoding a xenogeneic antigen molecule of 266 amino acid residues.The nucleotide sequences of the SLA-DRB genes,however,are different when compared either among the three strains or with the published data of SLA-DRB sequences,which allowed our novel SLA-DRB alleles receiving their accession numbers AY102479,AY102480 and AY102481 from the GenBank.This study further reveals that the phylogenic homologies of MHC DR or DR-like genes in structures of nucleotides and deduced amino acids between Chinese pigs(SLA)and human(HLA-DRB1*0901)are better than those between pigs and mice (H-2~b Eβ).High similarities were also found for DRα-DRβ heterodimers between Chinese pigs and human in terms of amino acids sequences critical for binding with human CD4 coreceptor molecule,which are better than those between SLA-DR and H-2 I-E molecules.A functional test indicated that,by cotransfection with Bm-DRA and Bm-DRB genes,the Bm-DR molecule-expressed L929 cells could stimulate human T cells quite well in a xenogeneic reaction in presence of human APCs.Cellular & Molecular Immunology.2004;1 (3):212-218.
基金Supported by Grant-in-Aid for Scientific Research From the Ministry of Education,Culture,Science and Technology of Japan,No.21K07054(Hironori Yoshiyama)and No.22K07101(Hisashi Iizasa).
文摘Epstein-Barr virus(EBV)-associated gastric cancer(EBVaGC)cells originate from a single-cell clone infected with EBV.However,more than 95%of patients with gastric cancer have a history of Helicobacter pylori(H.pylori)infection,and H.pylori is a major causative agent of gastric cancer.Therefore,it has long been argued that H.pylori infection may affect the development of EBVaGC,a subtype of gastric cancer.Atrophic gastrointestinal inflammation,a symptom of H.pylori infection,is observed in the gastric mucosa of EBVaGC.Therefore,it remains unclear whether H.pylori infection is a cofactor for gastric carcinogenesis caused by EBV infection or whether H.pylori and EBV infections act independently on gastric cancer formation.It has been reported that EBV infection assists in the oncogenesis of gastric cancer caused by H.pylori infection.In contrast,several studies have reported that H.pylori infection accelerates tumorigenesis initiated by EBV infection.By reviewing both clinical epidemiological and experimental data,we reorganized the role of H.pylori and EBV infections in gastric cancer formation.
文摘Objective Although HIV-1 infection is prevalent in many regions in China, it remains largely unknown on the biological characteristics of dominant circulating isolates. This study was designed to isolate the circulating viral strains from different prevalent regions and to characterize their biological properties and neutralization sensitivity. Methods Primary viruses were isolated from fresh PBMCs using the traditional co-culture method and their capacity of inducing syncytium was tested in MT-2 cells. Meanwhile, their coreceptor usage was determined with two cell lines: Magi and GHOST (3) stably expressing CD4 and the chemokine receptor CCR5 or CXCR4. Furthermore, the sensitivity of these viruses to neutralization by HIV-1-infected patients’ plasma which were highly active to neutralize SF33 strain, was quantified in GHOST cell-based neutralization assay. Results Six primary viral strains were isolated from 4 separated regions. Isolates LTG0213,LTG0214 and XVS032691 induced syncytia in MT-2 cells, and used CXCR4 as coreceptor. Isolates XJN0021, XJN0091, or SHXDC0041 did not induce syncytia, and used CCR5 as coreceptor. Overall neutralization sensitivity differed among four representative strains: HIV-1 XVS032691>LTG0214>XJN0091≈SHXDC0041. Conclusion The neutralization sensitivity of HIV isolates is linked with the phenotype of isolates, in which syncytium-inducing (SI) or CXCR4-tropic (X4) viruses are more easily neutralized than non-syncytium-inducing (NSI) or CCR5-tropic (R5) viruses. The genetic subtypes based on the phylogeny of env sequences are not classical neutralization serotypes.
