| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
Recent studies have indicated functional crosstalk between intestinal epithelial cells (IEC) and intestinal intraepithelial T cells (IEL). For instance, the absence of γδ-IEL but not αβ-IEL is associated with a significant reduction of IEC turnover and a downregulation of the expression of MHC class II molecules. We intercrossed γδ-IEL-deficient (δ^<-/->) and αβ-IEL-deficient (β^<-/->) mice to obtain wild-type (WT),δ^<-/->, β^<-/-> and double mutant (δxβ^<-/->) littermates and examined extensively the effect of γδ-IEL and/orαβ-IEL deprivations on the generation and differentiation of IEC.
In δ^<-/-> mice, the development of IEC was down-regulated. Taking this effect of γδ-IEL on IEC growth at face value, γδ-IEL are capable of accelerating the generation and differentiation of adjacent IEC (γδ-↑). In the complete absence of T cells in δxβ^<-/-> mice, however, the generation and differentiation of IEC were found to be unaltered. In view of these findings, αβ T cells residing in the intrae
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pithelial (αβ-IEL) and/or LP compartments may have the ability to decelerate the generation and differentiation of IEC (αβ-↓). Based on this concept, IEC growth remains almost the same in WT mice with γδ-↑/αβ-↓ activities and δ x β^<-/-> mice without γδ-↑/αβ-↓ activities and was down-regulated in δ^<-/-> mice that lack γδ-↑ activity but possess αβ-↓ activity. Then, why was it not up-regulated in β^<-/-> mice that possess γδ-↑ activity but lack αβ-↓ activity? We have previously demonstrated that the cytolytic and IFN-γ-producing activities of γδ-IEL were attenuated sharply in β^<-/-> mice, whereas that γδ-IEL were irrelevant to such activities of αβ-IEL. In this context, it is conceivable that the γδ-↑ activity of γδ-IEL is also dependent on αβ T cells and, therefore, drastically reduced in β^<-/-> mice. Whatever the functional link between γδ-↑ and αβ-↓ activities, we corroborated that the total disappearance of T cells does not exert any significant effect on the generation and differentiation of villous IEC. Less
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