Anti-TCRβ mAb induces long-term allograft survival by reducing antigen-reactive T cells and sparing regulatory T cells

Y. Miyahara, M. Khattar, P. M. Schroder, B. Mierzejewska, R. Deng, R. Han, W. W. Hancock, W. Chen, S. M. Stepkowski

Research output: Contribution to journalReview article

14 Scopus citations

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. This study shows that peri-transplant therapy with a T cell receptor-specific antibody induces long-term allograft survival in mice by selective reduction of antigen-reactive T cells while sparing regulatory CD4+Foxp3+ T cells.

Original languageEnglish (US)
Pages (from-to)1409-1418
Number of pages10
JournalAmerican Journal of Transplantation
Volume12
Issue number6
DOIs
StatePublished - Jun 2012

Keywords

  • Allograft survival
  • T cell receptor
  • T regulatory cells
  • tolerance

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

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