title: CD28 superagonist antibody treatment attenuated obliterative bronchiolitis in rat allo-orthotopic tracheal transplantation by preferentially expanding Foxp3-expressing regulatory T cells.
abstract: Obliterative airway disease (OAD) due to chronic alloantigen rejection remains a major challenge for long-term graft survival in lung transplantation. It is known that superagonistic CD28-specific monoclonal antibody JJ316 (supCD28 MAb) has the ability to induce regulatory T cells (Tregs) efficiently. Here we used a rat orthotopic tracheal transplantation model to investigate the effects of supCD28 MAb on expanding Tregs in vivo and its application in suppression of acute and chronic airway allograft rejection. SupCD28 MAb administration revealed a significant increase in the CD4+CD25+ T cells, CD4+FoxP3+ T cells, and CD4+CD25+ FoxP3+ T cells population among CD4+ T cells in spleen, peripheral blood, as well as cervical lymph nodes. The allografts from animals treated with supCD28 MAb showed significantly less airway obliteration and rejection of the respiratory epithelium compared with allografts of the mouse immunoglobulin G-treated group on the 5th day and the 60th day after transplantation. Overall, our data demonstrated that an intraperitoneally administrated low dose of supCD28 MAb was sufficient to induce Treg cell expansion in vivo and was effective in protecting the airway graft from early rejection and chronic OAD development. These findings provide the basis for new therapies to prevent OAD and perhaps rejection of allografts in other human transplantations.
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Tongji University School of Medicine, Shanghai East Hospital, Shanghai, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Shi
authors.forename: Y
authors.initials: Y
authors.lastname: Niu
authors.forename: H
authors.initials: H
authors.lastname: Cao
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.forename: S
authors.initials: S
authors.lastname: Jiang
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.forename: H
authors.initials: H
authors.lastname: Fan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001989:Bronchiolitis Obliterans / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D018106:CD28 Antigens / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006084:Graft Rejection / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D007155:Immunologic Factors / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D016377:Organ Transplantation / Q000009:adverse effects; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D014132:Trachea / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D055114:X-Ray Microtomography
chemical_list: D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D007155:Immunologic Factors; C568777:JJ 316