title: Anti-TCRβ mAb induces long-term allograft survival by reducing antigen-reactive T cells and sparing regulatory T cells.
abstract: TCR specific antibodies may modulate the TCR engagement with antigen-MHC complexes, and in turn regulate in vivo T cell responses to alloantigens. Herein, we found that in vivo administration of mAbs specific for mouse TCRβ (H57-597), TCRα or CD3 promptly reduced the number of CD4(+)  and CD8(+)  T cells in normal mice, but H57-597 mAb most potently increased the frequency of CD4(+) Foxp3(+)  Treg cells. When mice were injected with staphylococcal enterotoxin B (SEB) superantigen and H57-597 mAb, the expansion of SEB-reactive Vβ8(+)  T cells was completely abrogated while SEB-nonreactive Vβ2(+)  T cells remained unaffected. More importantly, transient H57-597 mAb treatment exerted long-lasting effect in preventing T cell responses to alloantigens, and produced long-term cardiac allograft survival (>100 days) in 10 out of 11 recipients. While Treg cells were involved in maintaining donor-specific long-term graft survival, T cell homeostasis recovered over time and immunity was retained against third party allografts. Moreover, transient H57-597 mAb treatment significantly prolonged survival of skin allografts in naïve recipients as well as heart allografts in skin-sensitized recipients. Thus, transient modulation of the TCRβ chain by H57-597 mAb exhibits potent, long-lasting therapeutic effects to control alloimmune responses.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Toledo Medical College, Toledo, OH, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Miyahara
authors.forename: M
authors.initials: M
authors.lastname: Khattar
authors.forename: P M
authors.initials: PM
authors.lastname: Schroder
authors.forename: B
authors.initials: B
authors.lastname: Mierzejewska
authors.forename: R
authors.initials: R
authors.lastname: Deng
authors.forename: R
authors.initials: R
authors.lastname: Han
authors.forename: W W
authors.initials: WW
authors.lastname: Hancock
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.forename: S M
authors.initials: SM
authors.lastname: Stepkowski
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008815:Mice, Inbred Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014181:Transplantation Immunology
chemical_list: D000911:Antibodies, Monoclonal; D016693:Receptors, Antigen, T-Cell, alpha-beta