Anti-TCR? 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 TCR? (H57-597), TCR? 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 V?8(+) T cells was completely abrogated while SEB-nonreactive V?2(+) 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 TCR? chain by H57-597 mAb exhibits potent, long-lasting therapeutic effects to control alloimmune responses.

SUBMITTER: Miyahara Y 

PROVIDER: S-EPMC3365620 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature