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 language | English (US) |
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Pages (from-to) | 1409-1418 |
Number of pages | 10 |
Journal | American Journal of Transplantation |
Volume | 12 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2012 |
Keywords
- Allograft survival
- T cell receptor
- T regulatory cells
- tolerance
ASJC Scopus subject areas
- Transplantation
- Immunology and Allergy
- Pharmacology (medical)