| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1986: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1985: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
The differentiation, growth regulation, and recognition mechanism of LGL (NK) were studied using murine cloned LGL lines.
1. Analysis of T cell receptor (TCR) genes: Southern blot analysis of DNA from LGL clones using <alpha> , <beta> , and <gamma> chain genes of TCR indicated that all of the lines had rearranged TCR genes. In most of LGL clones, mRNA for <alpha> , <beta> , and <gamma> chains were also detected. It was thus indicated that at least some of LGL definitely belonged to T cell lineage. The <beta> gene rearrangement patterns of lines, however, showed no correlation with the cytotoxic spectrum of them, suggesting that <alpha> <beta> complex of TCR was not involved in the recognition of tumor cells by these cells as opposed to T cells. Since some of LGL clones lacking <gamma> chain mRNA showed typical NK activity, it was also unlikely that <gamma> chain was involved in the recognition. Recently, it has been reported that some of human NK clones did express the second TCR, <gamma> <delta> complex. Although it is rather unlikely that such receptors are involved in NK recognition, the finding is certainly important in terms of NK cell differentiation, and is under the inrestigation in our murine LGL clones.
2. Analysis of IL 2 receptor (R) : All of the LGL lines were dependent on IL 2 for The persistent growth was obtained by the co-presence of macrophages (M <phi> ) or IL 1. Analysis of IL 2R by <^(125)I> -IL 2 binding assay indicated that the expression of high affinity IL 2R tended to decline with IL 2 alone, and that it was maintained in the presence of IL 2 and M <phi> . The results suggested that M <phi> played significant roles in the regulation of growth of LGL, most likely by maintaining the expression of functional IL 2R on them. Based on these findings, further investigations on the early differentiation as well as tumor recognition mechanism of LGL are now in the progress.
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