ABSTRACT
The study was aimed to investigate the effect of anti-mouse CD122 antibody on the hematopoietic repopulating capacity of cord blood CD34⁺ cells in a humanized murine model-non obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. After sublethal irradiation with γ-ray, NOD/SCID mice were intraperitoneally injected with 200 µg mouse isotype control antibody or anti-mouse CD122 antibody. Human cord blood CD34⁺ cells or phosphate-buffered saline (PBS) were injected via the tail vein at 6-8 hours later. Cohort of the mice injected with anti-mice CD122 antibody or control antibody alone were sacrificed at different time point (at week 2, 3, and 4 weeks) after the injection, and the percentage of NK cells in the peripheral blood was analyzed by flow cytometry. To evaluate the effect of anti-mouse CD122 antibody on the repopulating capacity of cord blood CD34⁺ cells in the recipient mice, phenotype analysis was performed in the bone marrow at 6 and 8 weeks after the transplantation. The results showed that the proportion of NK cells in the peripheral blood were (4.6 ± 0.6)% and (5.7 ± 1.7)% at week 2 and 3 after anti-CD122 antibody injection respectively,which decreased by 60%, compared with the mice injected with isotype control antibody. After 6 and 8 weeks of cord blood CD34⁺ cell transplantation,the percentage of human CD45⁺ in the bone marrow of the recipient mice treated with anti-mice CD122 antibody was (63.0 ± 12.2)% and (53.2 ± 16.3)%,respectively,which were dramatically higher than that in the mice treated with isotype control antibody (7.7 ± 3.6)% and (6.1 ± 2.4)%. Moreover,at 8 weeks after transplantation,human CD34⁺ cells appeared significantly in the recipients treated with anti-CD122 antibody. It is concluded that the anti-mouse CD122 antibody enhances the hematopoietic repopulating capacity of cord blood CD34⁺ cells in the NOD/SCID mice through decreasing the proportion of NK cells.
Subject(s)
Animals , Humans , Mice , Antibodies , Allergy and Immunology , Antigens, CD34 , Bone Marrow , Cord Blood Stem Cell Transplantation , Fetal Blood , Allergy and Immunology , Hematopoietic Stem Cell Transplantation , Hematopoietic System , Cell Biology , Allergy and Immunology , Interleukin-2 Receptor beta Subunit , Allergy and Immunology , Killer Cells, Natural , Mice, Inbred NOD , Mice, SCID , Transplantation, HeterologousABSTRACT
BACKGROUND: While a significant genetic predisposition to schizophrenia has been proposed, the mode of inheritance or nature of etiological factors is unknown. Previous reports of a genome-wide survey for schizophrenia susceptibility genes have indicated a possible region of linkage on chromosome 22. In order to test the possibility that the interleukin-2 recepto beta chain(IL-2R beta ) gene on chromosome 22 is of etiological importance in schizophrenia, a case-control association study was conducted. METHODS: Subjects were ninety-three schizophrenic patients with a diagnosis of schizophrenia by DSM- III -R criteria and ninety-seven normal controls. Schizophrenic patients were divided by clinical phenotypes such as DSM- III -R diagnostic subtypes, positive and negative symptoms, and family history so as to increase the homogeneity of schizophrenics. Genomic DNA was extracted from whole blood lymphocytes according to standard procedures. The DNA was used to study a dinucleotide repeat in the IL-2R beta gene. To reveal the dinucleotide polymorphism, genomic DNA of subjects was amplified by polymerase chain reactions(PCR). RESULTS: At the IL-2R beta gene locus, all the previously reported alleles (eight different alleles) of a dinucleotide polymorphism were identified. There was no significant difference between number of heterozygosity in schizophrenic patients and in normal controls. There was no significant difference in the distribution of frequencies of alleles between schizophrenics and normal controls. In addition, there was no significant difrfrence in the allele frequencies among subtypes of schizophrenic patients according to DSM- III -R diagnostic subtypes, positive and negative symptoms, and family history. CONCLUSIONS: The present study did not detect a difference in frequencies of alleles of a dinucleotide polymorphism at the IL-2R beta gene locus between schizophrenic patients and normal controls. These results do not support an evidence that IL-2R beta gene plays, a major role in the etiology of schizophrenia.