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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; Chen, Jibing; Shao, Wei; Xie, Baiyi; Wang, Yongzhi; Lan, Tianshu; Thorlacius, Henrik LU and Qi, Zhongquan (2010) In Immunological Investigations 39(8). p.807-819
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cardiac transplantation, Anti-CD44 mAb, CD4(+) memory T cells
in
Immunological Investigations
volume
39
issue
8
pages
807 - 819
publisher
Marcel Dekker
external identifiers
  • wos:000283076800003
  • scopus:77958165118
ISSN
0882-0139
DOI
10.3109/08820139.2010.497833
language
English
LU publication?
yes
id
db89ce13-62c4-4ff9-b490-8d09b1ee342b (old id 1720845)
date added to LUP
2010-12-03 14:09:37
date last changed
2018-05-29 11:24:13
@article{db89ce13-62c4-4ff9-b490-8d09b1ee342b,
  abstract     = {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.},
  author       = {Wang, Feng and Chen, Jibing and Shao, Wei and Xie, Baiyi and Wang, Yongzhi and Lan, Tianshu and Thorlacius, Henrik and Qi, Zhongquan},
  issn         = {0882-0139},
  keyword      = {Cardiac transplantation,Anti-CD44 mAb,CD4(+) memory T cells},
  language     = {eng},
  number       = {8},
  pages        = {807--819},
  publisher    = {Marcel Dekker},
  series       = {Immunological Investigations},
  title        = {Anti-CD44 Monoclonal Antibody Inhibits Heart Transplant Rejection Mediated by Alloantigen-primed CD4(+) Memory T Cells in Nude Mice},
  url          = {http://dx.doi.org/10.3109/08820139.2010.497833},
  volume       = {39},
  year         = {2010},
}