|Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
T cells play an important role in pathogenesis of bronchial asthma. However, it is not completely known the mechanism that circulating lymphocytes infiltrate into the airways of asthmatic patients. Since SCID mice are unable to reject xenogenic transplants, many xenotransplant models using various human tissues have been developed. Therefore, to examine the interaction between bronchi and T lymphocytes of asthma, it may be possible to use the human bronchial xenograft and PBMC xenograft in the SCID mice. We transplanted the human bronchi into the subcutaneum of SCID mice and intraperitoneally injected PBMCs which were obtained from asthmatic patients and normal subjects (asthmatic and normal huPBMC-SCID mice) There was no difference of the percentage of CDS, CD4, CD8, CD25, CD45RO, CD103, and CLA positive cells in PBMCs between asthmatic patients and normal subjects, and CD3-positive cells in peripheral blood of asthmatic and normal huPBMC-SCID mice. The number of CDS, CD4, CD8, CD45RO and CD103 positive cells in the xenografts of asthmatic huPBMC-SCID mice was higher than those of normal huPBMC-SCID mice. L-4 mRNA and IL-5 mRNA were significantly higher in the xenografts of asthmatic huPBMC-SCID mice than that in the xenografts of normal huPBMC-SCID mice, but there were no significant differences in the expressions of IL2 mRNA and IFN-g mRNA between the xenografts of asthmatic huPBMC-SCID mice and that of normal huPBMC-SCID mice. These data suggests that T cells, especially Th2 type T cells, of asthmatics preferentially infiltrate into the human bronchi.
In addition, we also investigated intra-epithelial T lymphocytes in human bronchi. In the epithelium, activated T cells was not increased but CD103 was increased compared to those in the lamina propria. In asthmatic bronchial epithelium, the number of CD4 was lower than that in non-asthmatic bronchial epithelium.