1997 Fiscal Year Final Research Report Summary
Induction of tolerance of contact hypersensitivity by blocking CD28 Signal
| Project/Area Number |
08670952
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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 |
Dermatology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
YOKOZEKI Hiroo Tokyo Med.Dental University, Associate professor, 医学部, 助教授 (90210608)
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| Co-Investigator(Kenkyū-buntansha) |
HATSUNAGA Tsuyoshi Tokyo Med.Dept of Dermatology, Assistant, 医学部, 助手 (50239050)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Langerhans cells / Contact allergy / B7 antigen / Cytokines / atopic dermatitis |
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| Research Abstract |
1) The B7 nolecules expression in AD and CD
In the present study, we investigated the expression and function of co-stimulatory molecules in AD and CD.These molecules were not detected in normal control subjects. In non-lesional skin of atopic dermatits, CD86 but not CD80 was detected. Inlesional atopic dermatits, CD80 was expressed 42%, while CD86 was expressed in all case. Similar results of the stronger expression of CD86 over CD80 was detected in the lesional skin in CD.We conducted the inhibition test. Anti-CD86 mab completely inhibite T cell proliferation stimulated with crude extract of DP in the epidermal cell as antigen presenting cells.
These data indicate that CD86 expressed on Langerhans cells may play an important part in the pathogenesis of AD and CD.
2) In vitro
The hapten, TNBS,induced weak B7-1 (CD80) and moderate B7-2 (CD86) expression on Langerhans cells and mRNA expression of both molecules in organ-cultured murine skin. The intradermal injection of haptenated EC induced hapten-specific contact sensitivity.
When hapten-treated EC were injected into mice after incubation with anti-B7-2 (CD86) or B7-1 (CD80) antibody the resultant contact sensitivity reaction was decreased to less than 50% of the control reaction. Anti-B7-2 and antiB7-1mAb also inhibited hapten-specific lymphocyte proliferation or the allogeneic mixed lymphocyte reaction in vitro.
These data indicated that costimulatory signals induced by a hapten on Langerhans cells play an important roles in the induction of contact sensitivity in mice.
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