title: Costimulation blockade inhibits the indirect pathway of allorecognition in nerve allograft rejection.
abstract: Nerve allografts provide a temporary scaffold for host nerve regeneration. The need for systemic immunosuppression limits clinical application. Characterization of the immunological mechanisms that induce immune hyporesponsiveness may provide a basis for optimizing immunomodulating regimens. We utilized wild-type and MHC class II-deficient mice, as both recipients and donors. Host treatment consisted of triple costimulatory blockade. Quantitative assessment was made at 3 weeks using nerve histomorphometry, and muscle testing was performed on a subset of animals at 7 weeks. Nerve allograft rejection occurred as long as either the direct or indirect pathways were functional. Indirect antigen presentation appeared to be more important. Nerve allograft rejection occurs in the absence of a normal direct or indirect immune response but may be more dependent on indirect allorecognition. The indirect pathway is required to induce costimulatory blockade immune hyporesponsiveness.
authors.affiliation: Department of Neurological Surgery, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Wilson Z
authors.initials: WZ
authors.lastname: Ray
authors.forename: Rahul
authors.initials: R
authors.lastname: Kasukurthi
authors.forename: Santosh S
authors.initials: SS
authors.lastname: Kale
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Santosa
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hunter
authors.forename: Philip
authors.initials: P
authors.lastname: Johnson
authors.forename: Ying
authors.initials: Y
authors.lastname: Yan
authors.forename: Thalachallour
authors.initials: T
authors.lastname: Mohanakumar
authors.forename: Susan E
authors.initials: SE
authors.lastname: Mackinnon
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Tung
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001369:Axons / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009416:Nerve Regeneration / Q000276:immunology; D010525:Peripheral Nerves / Q000276:immunology / Q000637:transplantation; D020426:Sciatic Neuropathy / Q000276:immunology / Q000601:surgery; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000637:transplantation; D023001:Transplantation Tolerance / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D019138:Antibodies, Blocking; D000949:Histocompatibility Antigens Class II