1990 Fiscal Year Final Research Report Summary
Analyses of T Cell Proliferation/Differentiation and Repertoire Selection in the thy Usus
| 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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| Project Period (FY) |
1989 – 1990
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| Keywords | Thymic stromal cells / Iutrathymic T cell proliferation Hifferentiation / T cell repertoire / Thymic selection / T cell growth factor |
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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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[Publications] Utsumi, K., Sawada, M., Narumiya, S., Nagamine, J., Sakata, T., Iwagami, S., Kita, Y., Teraoka, H., Hirano, H., Ogata, M., Hamaoka, T., and Fujiwara, H.: "Adhesion of immature thymocytes to thymic stromal cells through fibronectin molecules and its significance for the induction of thymocyte differentiation." Proc. Natl. Acad. Sci. USA.
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kimura, K., Matsubara, H., Sogoh, S., Kita, Y., Sakata, T., Nishitani, Y., Watanabe, S., Hamaoka, T., and Fujiwara, H.: "The role of glycosaminoglycans in the regulation of T cell proliferation induced by thymic stroma-derived T cell growth factor" J. Immunol.
Description
「研究成果報告書概要(欧文)」より
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[Publications] Matsubara, H., Kosaka, H., Sogo, S., Maruo, S., Sugihara, S., Asano, Y., Kohno, Y., Kimoto, M., Suzuki, G., Ishimura, K., Fujita, H., Hamaoka, T., and Fujiwara, H.: "T cell clones are killed by a thymic stromal cell monolayer following stimulation of T cell receptor with antigen and/or H-2 molecules on the monolayer" International Immunology. 2 :. 755-763 (1990)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kosaka, H., Matsubara, H., Sogoh, S., Ogata, M., Hamaoka, T., and Fujuwara, H.: "An in vitro model for cyclosporin A-induced interference of intrathymic clonal elimination" J. Exp Med. 172 :. 395-398 (1990)
Description
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[Publications] Tatsumi, Y., Kumanogoh, A., Saitoh, M., Mizushima, Y., Kimura, K., Suzuki, S., Yagi, H., Horiuchi, A., Ogata, M., Hamaoka, T., and Fujiwara, H.: "Differentiation of thymocytes from CD3^-4^-8^- through CD3^-4^-8^+ into more mature stages induced by a thymic stromal cell clone." Proc. Natl. Acad. Sci. USA. 87. 2750-2754 (1990)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Fujiwara, H., Ogata, M., Mizushima, Y., Tatsumi, Y., Takai, Y., and Hamaoka, T.: "Proliferation and differentiation of immature thymocytes induced by a thymic stromal cell clone" Thymus. 16 :. 159-172 (1990)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Sakata, T., Iwagami S., Tsuruta, Y., Teraoka, H., Tatumi, Y., Kita, Y., Nishikawa, S., Takai, Y., and Fujiwara, H.: "Constitutive expression of interleukin-7 (IL-7) mRNA and production of IL-7 by a cloned murine thymic stromal cell line" J. Leukocyte Biol. 48 :. 205-212 (1990)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kosaka, H., Ogata, M., Sano, H., Sakuma, S., Mizuhsima, Y., Nakamura, E., Teraoka, H., Hamaoka, T., and Fujiwara, H.: "Thymic stroma-derived T cell growth factor (TSTGF). III. Its ability to promote T cell proliferation without stimulating interleukin 2- or 4-dependent autocrine mechanism" J. Leukocyte Biol. 47. 121-128 (1990)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Mizushima, Y., Saitoh, M., Ogata, M., Kosaka, H., Tatsumi, Y., Kiyotaki, C., Hamaoka, T., and Fujiwara, H.: "Thymic stroma-derived T cell growth factor (TSTGF). IV. The capacity of TSTGF to promote the growth of L3T4 Lyt-2 thymocytes by synergy with phorbor myristate acetate or various interleukins" J. Immunol. 142. 1195-1202 (1989)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kosaka, H., Ogata, M., Hikita, I., Maruo, S., Sugihara, S., Matsubara, H., Takai, Y., Hamaoka, T., and Fujiwara, H.: "A model for the clonal elimination in the thymus" Proc. Natl. Aca. Sci. USA. 86. 3773-3777 (1989)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Fujiwara, H., Ogata, M., Mizushima, Y., Kosaka, H., Matsubara, H., Takai, Y., and Hamaoka, T.: "Thymic stroma-derived T cell growth factor : Its role in the growth of immature thymocytes and T cell repertoire selection" Proc. of 19th Internatl. Symposium of the princess Takamatsu Cancer Res. Fund. 115-126 (1989)
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「研究成果報告書概要(欧文)」より
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[Publications] Oqata, M., Matsubara, H., Takai, Y., Kosaka, H., Katagiri, T., Sano, H., Ishimura, K., Fujita, H., Hamaoka, T., and Fujiwara, H.: "Capacities of a newly established thymic stromal cell clone to express Ia antigens and to produce interleukin 6, colony-stimulating factor and thymic stroma-derived T cell growth factor" J. Leukocyte Biol. 45. 69-78 (1989)
Description
「研究成果報告書概要(欧文)」より
