title: Foxp3-expressing regulatory T cells expanded with CD28 superagonist antibody can prevent rat cardiac allograft rejection.
abstract: BACKGROUND
  It is well known that CD4(+)CD25(+) regulatory T (Treg) cells play a central role in the suppression of autoimmunity, inflammation and allograft rejection. Therefore, therapeutic agents that capable of enhancing the number and activity of this T-cell subset are highly desirable.
  
  
  METHODS
  The present study was designed to investigate the effects of superagonistic CD28-specific monoclonal antibody (supCD28 MAb) on preferentially expanded rat naturally occurring CD4(+)CD25(+) Treg (nTreg) cells and its applicability in cardiac transplantation.
  
  
  RESULTS
  A single administration of supCD28 MAb preferentially proliferated nTreg cells. The increase of Foxp3 expression and polarization toward a Th2 cytokine profile correlated with decreased production of interferon-gamma and increased production of interleukin-4 and -10 in the expanded CD4(+)CD25(+) Treg subset, which was capable of suppressing CD4(+)CD25(-) T-cell proliferation after purification. Furthermore, supCD28 MAb administration revealed that nTreg cells were preferentially proliferating in vivo and recruited into the grafts, resulting in significant prolongation of full MHC-mismatch cardiac graft survival.
  
  
  CONCLUSIONS
  Our data demonstrate that supCD28 MAb targets expansion of nTreg cells in vivo and maintains and enhances their regulatory functions, which represents a major advance toward the therapeutic use of polyclonally activated Treg cells as cellular therapy for treatment of allograft rejection.
authors: Laboratory of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors: Yusuke
authors: Y
authors: Kitazawa
authors: Masayuki
authors: M
authors: Fujino
authors: Takatoshi
authors: T
authors: Sakai
authors: Haruhito
authors: H
authors: Azuma
authors: Hiromitsu
authors: H
authors: Kimura
authors: Yoshitaka
authors: Y
authors: Isaka
authors: Shiro
authors: S
authors: Takahara
authors: Thomas
authors: T
authors: Hünig
authors: Ryo
authors: R
authors: Abe
authors: Xiao-Kang
authors: XK
authors: Li
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001773:Blood Cells / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D007519:Isoantigens / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011184:Postoperative Period; D051381:Rats; D011919:Rats, Inbred Strains; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors; D016042:Transplantation, Heterotopic
chemical_list: D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D053645:Interleukin-2 Receptor alpha Subunit; D007378:Interleukins; D007519:Isoantigens; D003208:Concanavalin A