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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Miyahara, Y; Khattar, M; Schroder, PM; Mierzejewska, B; Deng, R; Han, R; Hancock, WW; Chen, W; Stepkowski, SM

Published Date

  • June 2012

Published In

Volume / Issue

  • 12 / 6

Start / End Page

  • 1409 - 1418

PubMed ID

  • 22420295

Pubmed Central ID

  • 22420295

Electronic International Standard Serial Number (EISSN)

  • 1600-6143

International Standard Serial Number (ISSN)

  • 1600-6135

Digital Object Identifier (DOI)

  • 10.1111/j.1600-6143.2012.04006.x

Language

  • eng