Immunological functions of CD4^+ regulatory T cells induced by 4C8-costimulation
| Project/Area Number |
14570425
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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 |
内科学一般
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| Research Institution | Jichi Medical School |
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Principal Investigator |
MASUYAMA Jun-ichi Jichi Medical School, Div.of Internal Medicine, assistant professor, 医学部, 講師 (20165731)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | anti-4C8Ab / costimulation / regulatoy T cell / cytolcine / 4C8 / 樹状細胞 |
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| Research Abstract |
CD4^+CD25^+ regulatory T (Treg) cells naturally occur in mice and humans, and similar Treg cells can be induced in vivo and in vitro. However, the molecular mechanisms that mediate the generation of these Treg cell populations remain unknown. We previously described anti-4C8 monoclonal antibodies that inhibit the post-adhesive transendothelial migration of T cells through human endothelial cell monolayers. We demonstrate here that Treg cells are induced by costimulation of CD4^+ T cells with anti-CD3 plus anti-4C8. The costimulation induced full activation of CD4^+ T cells with high levels of IL-2 production and cellular expansion that were comparable to those obtained on costimulation by CD28. However, upon restimulation, 4C8-costimulated cells (4C8 Treg cells) produced high levels of IL-10 but no IL-2 or IL-4, and maintained high expression levels of CD25 and intracellular CDI 52, as compared to CD28-costimulated cells. The former cells showed hyporesponsiveness to anti-CD3 stimulation and suppressed the activation of bystander T cells depending on cell contact but not IL-10 or TGF-β The suppressor cells developed from CD4^+CD25^+CD45RO^+ cells. IL-7 and IL-15 promoted proliferation of 4C8 Treg cells. 4C8 Treg cells inhibited activation of CD4^+T cells in response to coculture with dendritic cells developed from peripheral blood monocytes. The results suggest that 4C8 costimulation induces the generation of Treg cells that share phenotypic and functional features with CD4^+CD25^+ T cells, and that CD25 memory T cells may differentiate into certain Treg cell subsets in the periphery. Furthermore, 4C8 Treg cells may have potential to suppress allo-rejective response due to organ transplantation.
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Report
(3 results)
Research Products
(4 results)
