1990 Fiscal Year Final Research Report Summary
Analysis of the Biological Function of CD5 Molecule.
| Project/Area Number |
63480170
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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 | Kyushu University |
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Principal Investigator |
NISHIMURA Yasuharu Department of Genetics, Medical Institute of Bioregulation, Kyushu University, Associate Professor, 生体防御医学研究所, 助教授 (10156119)
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| Co-Investigator(Kenkyū-buntansha) |
KIMURA Akinori Department of Genetics, Medical Institute of Bioregulation, Kyushu University, R, 生体防御医学研究所, 助手 (60161551)
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| Project Period (FY) |
1988 – 1990
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| Keywords | CD5 molecule / T cell activation / Mutant cell / Retroviral vector / Gene transfection / Interleukin 1 |
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| Research Abstract |
In order to define biological function of the CD5 (T1, Leu1, Tp67) molecule, a cDNA clone of CD5 was expressed in a CD5 deficient Jurkat cell line and in a murine T cell hybridoma. A Jurkat subclone (Jurkat 9.9) produced interleukin-2 (IL-2) in response to anti-CD3 monoclonal antibody (MAB) crosslinked to solid support. IL-2 production was enhanced by co-culture with the anti-CD5 MAb OKT1. A CD5 deficient mutant clone Jurkat 1.15 was generated by treatment with ethyl methanesulfonate followed by selection with anti-CD5 MAb plus complement. Jurkat 1.15 did not demonstrate enhancement of IL-2 production by OKT1 in the presence of crosslinked anti-CD3 MAb. A cDNA encoding CD5 was introduced into a defective retrovirus which was used to infect Jurkat 1.15. A Jurkat clone stably expressing CD5 was established. In response to OKT1, a rise in intracellular calcium was observed in both the parent Jurkat 9.9 and the CD5 positive infectant but not in the CD5 negative mutant or a G418 resistant c
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ontrol. Furthermore, expression of CD5 restored the augmentation of Il-2 production by OKT1 in response to crosslinked anti-CD3 MAb. A murine T cell hybridoma By155.16 which produces IL-2 in response to HLA-DR antigens was also infected with the CD5 recombinant retrovirus and three stable CD5 positive infectants were generated. These hybridomas showed enhancement of Il-2 production by stimulation with OKT1 in the presence of suboptimal concetrations of soluble anti-murine CD3 MAb. These results provide further evidence that CD5 provides a costimulatory signal for T cell activation.
The role of the CD5 surface molecule in T cell responsiveness to interleukin-1 (IL-1) was examined. The CD5+ wild type Jurkat 9.9 produced interleukin-2 (IL-2) in response to anti-CD3 monoclonal antibocy (MAb), OKT3, crosslinked to a solid surface. IL-2 production was enhanced by co-culture with IL-1 or anti-CD5 MAb. Neither the CD5- mutant nor the CD5- G418-resistant infectant responded to anti-CD5 MAb or to IL-1. Responsiveness to IL-1 was restored by cell surface expression of CD5 in the CD5+ infectant. Both the CD5+ wild type Jurkat and the CD5+ infectant responded equivalent to purified IL-1, recomvinant IL-1alpha and recobinant IL-1beta. Optimal concentrations of IL-1and anti-CD5 MAb had an additive effect upon the enhancement of IL-2 production stimulated with crosslinked anti-CD3 MAb suggesting that IL-1 and CD5 act through distinct pathways. The specific binding of recombinant IL-1beta was examined in these cell lines. Both the specific binding (at 4ﾟC) and subsequent internalization (at 37ﾟC) of 125I labeled recombinant IL-1beta was equivalent in the CD5+ infectant and the CD5+ wild type Jurkat cell, whereas specific binding of ^<125>I labeled recombinant I1-1beta was markedly decreased in the CD5- G418-resistant infectant. These observations strongly suggest that cell surface expression of CD5 regulates binding of and responsiveness to IL-1. Less
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Research Products
(41 results)
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[Publications] Nishimura, Y., Bierer, B. E., Jones, W. K., Jones, N. H., Strominger, J. L., and Burakoff, S. J.: "Expression and function of a CD5 cDNA in human and murine T cells." European Journal of Immunology. 18. 747-753 (1988)
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「研究成果報告書概要(欧文)」より
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[Publications] Sasazuki, T., Kamikawaji, N., Fujisawa, K., Yoshizumi, H., Yasunami, M., Kimura, A., and Nishimura, Y.: "Differential roles of HLA-DR and DQ in immune regulation" Progress in Immunology Vll, Springer verlag, Berlin. 7. 853-860 (1989)
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「研究成果報告書概要(欧文)」より
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[Publications] Honda, K., Tamai, H., Morita, T., Kuma, K., Nishimura, Y., and Sasazuki, T.: "Hashimoto thyroiditis and HLA in Japanese" Clinical Endocrinology and Metabolism. 69. 1268-1273 (1989)
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[Publications] Sasazuki, T., Kikuchi, I., Hirayama, K., Matsushita, S., Ohta, N., and Nishimura, Y.: "HLA-linked immune suppression in humans." Immunology, Supplement. 2. 21-24 (1989)
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「研究成果報告書概要(欧文)」より
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[Publications] Fukui, Y., Nishimura, Y., Iwanaga, T., Kimura, A., Inamitsu, T., Hanaoka, Y, Kitagawa, T., and Sasazuki, T.: "Glycosuria and insulitis in NOD mice expressing the HLA-DQw6 molecule" Journal of Immunogenetics. 16. 445-453 (1989)
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「研究成果報告書概要(欧文)」より
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[Publications] Sasazuki, T., Iwanaga, T., Inamitsu, T., Yanagawa, Y., Yasunami, M., Kimura, A. Hirokawa, K., and Nishimura, Y.: "Expression and function of human major histocompatibility complex HLA-DQw6 genes in the C57BL/6 mouse." Cold Spring Harbor Symposium on Quantitative Biology. 54. 513-520 (1990)
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[Publications] Nishimura, Y., Iwanaga, T., Inamitsu, T., Yanagawa, Y., Yasunami, M., Kimura, A., Hirokawa, K., and Sasazuki, T.: "Expression of human major histocompatibility complex, HLA-DQw6 genes alters the immune response in C57BL/6 mice." Journal of Immunology. 145. 353-360 (1990)
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「研究成果報告書概要(欧文)」より
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[Publications] Nagafuchi, S., Kashiwagi, S., Okada, K., Anzai, K., Nakamura, M., Nishimura, Y., Sasazuki, T., and Niho, Y.: "Reversal of non-responders and postexposure prophylaxis by intradermal hepatitis B vaccination in Japanese medical personnel." Journal of American Medical Association.
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[Publications] Kamikawaji, N., Fujisawa, K., Yoshizumi, H., Fukunaga, M., Yasunami, M., Kimura, A., Nishimura Y., and Sasazuki, T.: "HLA-DQ restricted CD4^+ T cells specific to streptococcal antigen exist in low responders but not in high responders." Journal of Immunology.
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