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Anti-CD44 Monoclonal Antibody Inhibits Heart Transplant Rejection Mediated by Alloantigen-primed CD4(+) Memory T Cells in Nude Mice
- Wang, Feng (author)
- Chen, Jibing (author)
- Shao, Wei (author)
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- Xie, Baiyi (author)
- Wang, Yongzhi (author)
- Lan, Tianshu (author)
- Qi, Zhongquan (author)
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- (creator_code:org_t)
- 2010-08-18
- 2010
- English.
- In: Immunological Investigations. - : Informa UK Limited. - 0882-0139 .- 1532-4311. ; 39:8, s. 807-819
- Journal article (peer-reviewed)
Abstract
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- Donor-reactive CD4(+) memory T cells threaten the survival of transplanted organs. In this study, we used anti-CD44 monoclonal antibody (mAb) to inhibit adoptively transferred B6-reactive CD4(+) memory T cells (BALB/c origin) and to induce tolerance of B6 hearts in nude mice. The median survival time (MST) of the grafts was 6 days in the isotype group, and more than 100 days in the group treated with 8 doses of anti-CD44 at four-day intervals. Histological analysis revealed that the mean rejection level was Grade 3 in the isotype group, and Grade 0 or 1 in the multi-dose anti-CD44 treatment group. Compared with the isotype group, the multiply treated anti-CD44 group had significantly decreased IL-2 and IFN-gamma expressions, while IL-10 and TGF-beta were increased in the serum and the graft. Foxp3 in the graft was also increased. These data demonstrate that alloreactive CD4(+) memory T cells mediate the destruction of allografts, and the adhesion molecule CD44 plays an important role in this course. Anti-CD44 mAb may promote the reduction of CD4(+) memory T cells and the production of regulatory T cells (Tregs). Furthermore, Tregs are maintained at a certain level while suppressing cellular immunity and inducing the grafts long-term survival in transplant recipients.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kirurgi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Surgery (hsv//eng)
Keyword
- Cardiac transplantation
- Anti-CD44 mAb
- CD4(+) memory T cells
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- art (subject category)
- ref (subject category)
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- Shao, Wei
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- Lan, Tianshu
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- Lund University
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