title: Combination of antibodies inhibits accelerated rejection mediated by memory T cells in xenoantigen-primed mice.
abstract: BACKGROUND
  Donor-reactive memory T cells are known to accelerate allograft rejection; in our previous study, we reported that combined monoclonal antibodies (mAbs) could prolong islet allograft survival in alloantigen-primed mice. In this study, we examine the effects of donor-reactive memory T cells on the xenograft survival and methods to prolong the islet graft survival.
  
  
  METHODS
  To collect donor-reactive T cells, we performed full-thickness rat skin xenografting on BALB/c mice and isolated the T cells from the mice after 6-8 weeks. These cells were then adoptively transferred to syngenic mice 1 day before rat-to-mouse islet transplantation. Three experimental groups were established in the adoptive transfer model: recipient mice treated with isotype mAbs (isotype group); mice treated with anti-CD40L mAb (anti-CD40L group); and mice treated with anti-CD40L, anti-OX40L, and anti-CD122 mAbs (3-combined group).
  
  
  RESULTS
  Lewis rat islet xenografts transplanted in naïve mice showed a mean survival time (MST) of 12.8 days, while the graft rejection was accelerated if the recipient mice were treated with adoptively transferred donor-reactive T cells (MST, 8.67 days). Treatment with anti-CD40L mb could not reverse the accelerated rejection (MST, 9.3 days). However, when anti-CD40L mb was combined with anti-OX40L and anti-CD122 mAbs, there was a considerable increase in the MST, which was 72.2 days. Compared to the isotype group, the 3-combined group had significantly lesser proportion of memory T cells and greater proportion of regulatory T cells (Tregs) in the spleen. Meanwhile, in the 3-combined group, the production of anti-rat antibodies was markedly inhibited.
  
  
  CONCLUSIONS
  Treatment with a combination of antibodies could significantly reverse the accelerated rejection mediated by donor-reactive memory T cells by inhibiting cellular and humoral immune responses.
authors.affiliation: Organ Transplantation Institute of Xiamen University, Xiamen City, Fujian Province, China.
authors.forename: Feiyu
authors.initials: F
authors.lastname: Wang
authors.forename: Junjie
authors.initials: J
authors.lastname: Xia
authors.forename: Jibing
authors.initials: J
authors.lastname: Chen
authors.forename: Yuanzheng
authors.initials: Y
authors.lastname: Peng
authors.forename: Panpan
authors.initials: P
authors.lastname: Cheng
authors.forename: Henrik
authors.initials: H
authors.lastname: Ekberg
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wang
authors.forename: Zhongquan
authors.initials: Z
authors.lastname: Qi
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D015478:Antigens, Heterophile / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000906:Antibodies; D015478:Antigens, Heterophile