| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Ectodermal dysplasia and immunodeficiency syndrome (EDA-ID) is caused by NF-κB related genes abnormalities, and we specifically collected 6 EDA-ID patients due to NEMO abnormalities and analyzed how NEMO protein affects human T cells development. We have found one patient with reversion mosaicism of NEMO gene with 4.4 kb duplication. The patient PBMC showed different expression levels of NEMO among cell lineages. In PBMC, CD4+ T cells number was low with normal TCR Vβ usages, while CD8+ T cells number was normal with much skewed ICR Vβ usages, which indicated T cells development was impaired. The majority of both CD4+ and CD8+ T cells had normal level of NEMO, although monocytes, neutrophil, and the majority of B cells had much reduced level of NEMO. These results suggested that T cells with much reduced NEMO were disadvantageous in terms of development, differentiation, and/or survival.
On the other hand, we have analyzed 5 non-mosaicism EDA-ID patients with hypomorphic mutation of NEMO. The analysis of PBMC showed normal T cells number and TCRVβ usages in both CD4+ and CD8+ T cells. We have developed intracellular staining of NEMO by flow cytometry, which showed that the expression level of NEMO in the mosaicism patient was extremely low in comparison with those in non-mosaicism patients. It suggested that human T cells development, differentiation, and/or survival are impaired in the absence of NEMO, although hypomorphic NEMO causing EDA-ID would be enough for almost normal T cells developments.
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