| Project/Area Number |
01480190
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | Osaka University Medical School |
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Principal Investigator |
FUJIWARA Hiromi Osaka University Medical School Associate Professor, 医学部, 助教授 (70116094)
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| Co-Investigator(Kenkyū-buntansha) |
高井 康之 大阪大学, 医学部, 助手 (10216608)
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| Project Period (FY) |
1989 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1990: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1989: ¥4,000,000 (Direct Cost: ¥4,000,000)
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| Keywords | Thymic stromal cells / Iutrathymic T cell proliferation Hifferentiation / T cell repertoire / Thymic selection / T cell growth factor / thymus selection / 胸腺細胞の分化成熟 / T細胞レパ-トリ-形成 |
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| Research Abstract |
A newly established thymic stromal cell clone, MRL104.8a exhibited capacities to express Ia antigens and to support the growth of antigenspecific, interleukin-2 (IL-2) -dependent helper T cell (Th) clones without requirement of antigen and exogenous IL-2. The monolayer of this stromal cell clone exhbited the capacity to maintain immature double-negative thymocytes. Such capacity was also expressed by a factor produced by the MRL104.8a monolayer. This factor designated as Thymic Stroma-derived T cell Growth Factor (TSTGF) was found to be distinct from IL-2 or IL-4 but similar to IL-7 of the previously described cytokines from the functional and molecular aspects. The MRL104.8a monolayer also exerted its defferentiation-promoting effect on double-negative thymocytes. Culture for one day of purified double-negative thymocytes on the monolayer resulted in the induction of an appreciable percent of CD3 4 8 cells. This differentiation could also be induced by a semipurifid TSTGF sample but n
… More
ot by recombinant IL-7, suggesting that the MRL104.8a cells elaborate a factor (s) responsible for initiating the differentiation of doublenegative cells in addition to the growth-promotion factor identical or closely related to IL-7. When the culture period of double-negative thymocytes was extended to 2 or 3 days, an appreciable number of doublepositive (CD4^+8^+) and single-positive (CD4^+8^-) cells were generated on the MRL104.8a monolayer. The data were also presented that our thymic stromal cells could coutribute to the clonal elimination in the thymus. The growth of a Th clone, 9-16, was supported on the TSTGF-producing and la-expressing MRL104.8a monolayer in the absence of the antigen against which this Th clone is directed. In contrast, the presence of
the relevant antigen in the MRL104.8a culture elicited the lethal growth-inhibition of Th clone cells. Thus, these observations provide strong support for the proposition that a specialized thymic stromal component plays an essetial role in the intrathymic T cell development in the context of T cell growth and differentiation as well as T cell repertoire selection. Less
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