1999 Fiscal Year Final Research Report Summary
Molecular mechanisms for the regulation of T cell signals by sphingoglycolipids
| Project/Area Number |
10670118
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
FURUKAWA Keiko Nagoya University, Sch. of Med., Research Asociate, 医学部, 助手 (50260732)
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| Co-Investigator(Kenkyū-buntansha) |
FURUKAWA Koichi Sch. of Med., Professor, 医学部, 教授 (80211530)
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| Project Period (FY) |
1998 – 1999
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| Keywords | sphingoglycolipid / ganglioside / GM2 / GD2 synthase / knock-out mouse / T cell / signal transduction / interleukin-2 |
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| Research Abstract |
T cell development and function in complex ganglioside-lacking (GM2/GD2 synthase gene-disrupted) mice were analyzed. GM1, asialo-GM1 and gGD1b were representative gangliosides expressed on T cells of the wild type mice, and completely detected on those of mutant mice. The sizes and cell numbers of the mutant mice spleen and thymus were apparently reduced. When spleen cells were cultured with interleukin-2 (IL-2), those from the mutant showed reduced proliferation compared to those from the wild type. In contrast, proliferation by stimulation with concanavalin A or anti-CD3 cross-linking did not exhibit definite differences. Expression levels of IL-2 receptor α, β and γ were almost equivalent, and up-regulation of α chain after T cell activation were also similar between the mutant and wild type mice. Activation of JAK1, JAK3 and STAT5 after IL-2 treatment was reduced, and c-fos expression was delayed and reduced in the spleen cells of the mutant, suggesting that the IL-2 signal was attenuated in the mutant mice probably due to the modulation of the function of IL-2 receptors by the lack of complex gangliosides.
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