title: Specific immunosuppression by mixed chimerism with bone marrow transplantation after Staphylococcal Enterotoxin B pretreatment could prolong corneal allograft survival in mice.
abstract: OBJECTIVE
  We assessed the combined use of Staphylococcal Enterotoxin B (SEB) superantigen pre-treatment along with allogeneic bone marrow transplant (BMT) to induce immune suppression condition and inhibit corneal keratoplasty rejection in mice.
  
  
  METHODS
  BALB/C (H-2d) mice were both BMT and corneal allografts donors and C57BL/6(H-2b) mice were recipients. Prior to BMT, recipients received single injections of either SEB, cyclophosphamide (CYP), or normal saline (NS). Allogenic corneal penetrating keratoplasty was performed 7 days after BMT. Bone marrow chimerisms in recipients (donor major histocompatibility complex-II H2-d) were determined on Days 14, 28, and 56 post-BMT. Recipient immune response was assessed by mixed lymphocyte reactions (MLR) using splenocytes from C57BL/6 mice as responders in co-culture with stimulator cells from C57BL/6 (isogeneic), BALB/C (allogeneic), or CBA/1(third party) mice. Cluster of differentiation 4 receptors positive (CD4+) and CD8+T cells in recipient mice were evaluated. Corneal graft survival was assessed using Kaplan-Meier survival curves.
  
  
  RESULTS
  SEB pre-treatment induced higher levels of hematopoietic chimerism on Days 14, 28 and 56 post-BMT than did CYP or NS pre-treatment. Mean corneal allograft survival was significantly prolonged with group SEB-BMT (20.3±7.6 days) compared to group CYP-BMT (13.0±4.0 days) and NS-BMT (9.0±2.2 days). SEB-BMT mice splenocytes had diminished MLR responses compared to CYP-BMT or NS-BMT mice. CD4+ and CD8+ T cells in peripheral blood and spleens were significantly reduced in group SEB-BMT mice.
  
  
  CONCLUSIONS
  BMT after SEB pre-treatment could promote mixed chimerism, which inhibited allogeneic cornea transplant rejection. This should possibly relate to CD4+ and CD8+ T cell deletion and acquiring donor-specific immunosuppression.
authors.affiliation: Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Science Key Lab, Beijing, China.
authors.forename: Yingnan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Pan
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Jie
authors.forename: Yan
authors.initials: Y
authors.lastname: He
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D018920:Coculture Techniques; D003315:Cornea / Q000276:immunology* / Q000601:surgery; D016039:Corneal Transplantation; D003520:Cyclophosphamide / Q000008:administration & dosage; D004768:Enterotoxins / Q000008:administration & dosage*; D005260:Female; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects; D007165:Immunosuppression Therapy / Q000379:methods; D053208:Kaplan-Meier Estimate; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018089:Superantigens / Q000008:administration & dosage*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018183:Transplantation Chimera / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous
chemical_list: D004768:Enterotoxins; D018089:Superantigens; C031818:enterotoxin B, staphylococcal; D003520:Cyclophosphamide