| Project/Area Number |
12670418
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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 | The University of Tokyo |
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Principal Investigator |
HOSONO Osamu Institute of Medical Science, The University of Tokyo, Assistant Professor, 医科学研究所, 助手 (50190210)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | T cells / CD26 / dopeptidyl peptidase IV / immune response |
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| Research Abstract |
CD26 is a T cell costimulatory molecule with dipeptidyl peptidase IV (DPPIV) enzyme activity in its extracellular region. and preferentially expressed on a subset of CD4+ memory T cells. DPPIV enzyme activity has been shown to play a critical role in CD26 mediated immune response.
1. Mechanism of enhanced T cell memory response by soluble CD26 : Recombinant soluble CD26 (rsCD26) could enhance in vitro antigen induced proliferative T cell response. rsCD26 up regulated the expression of the costimulatory molecule CD86 on CD14+ monocytes through its DPPIV activity. In addition, we demonstrated that mannose-6 phosphate/insuline-like growth factor II receptor played a role in transporting rsCD26 into the monocytes.
2. Production of soluble CD26 from T cells : Soluble CD26 was released from T cells activated with PHA or anti-CD3+anti-CD28 stimulation, which was enhanced by IL-2 addition. Serum levels of sCD26 as well as its specific DPPIV activity were significantly decreased in SLE and were inversely correlated with overall disease activity and positively with number of CE26+ cells. Serum levels of sCD26 may be involved in the pathophysiology of SLE.
3. Analysis of regulatory factors for DPPIV enzyme activity : We could not found anti-CD26 autoantibody in serum from various patients and normal individuals by Western blot analysis. Further precise studies might be necessary. We demonstrated that binding of the soluble anti-CD26 monoclonal antibody inhibits human T cell growth and proliferation by inducing G1 arrest, which is associated with enhancement of p21^<Cip1> expression through activation of ERK pathway. This effect depends on the DPPIV enzyme activity of the CD26 molecule. These data suggest that anti-CD26 treatment may have potential use in the clinical setting involving activated T cell dysregulation, including GVHD and SLE.
We plan to clarify the regulatory mechanism of memory response through memory T cell related molecules including CD26, GD3, and CD82.
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