Blocking the common gamma-chain of cytokine receptors induces T cell apoptosis and long-term islet allograft survival. Academic Article uri icon

Overview

abstract

  • The common gammac-chain is an essential signaling component shared by all known T cell growth factor (TCGF) receptors (i.e., IL-2, IL-4, IL-7, IL-9, and IL-15). In the present study, we have studied the effect of gammac-chain blockade on T cell activation and allograft rejection. Treatment of B6AF1 (H-2b/d.k) recipient mice with anti-gammac mAbs induced long-term survival of DBA/2 (H-2d) islet allografts (>150 days, n = 8), whereas control Ab-treated mice rejected the islet allografts within 17 days (n = 6). The state of engraftment induced by the anti-gammac mAbs was remarkably stable, as recipient mice bearing the primary islet allografts accepted a second DBA/2 islet allograft without further immunosuppression and systemic administration of high doses of IL-2Ig fusion protein failed to provoke rejection. Blocking the gammac-chain inhibited T cell proliferation and induced T cell apoptosis by repressing expression of Bcl-2. Our data suggest that one means of inducing T cell apoptosis and stable allograft survival can be achieved via gammac-chain blockade.

publication date

  • February 1, 2000

Research

keywords

  • Antibodies, Blocking
  • Apoptosis
  • Graft Survival
  • Islets of Langerhans Transplantation
  • Receptors, Cytokine
  • T-Lymphocytes

Identity

Scopus Document Identifier

  • 0005618532

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.164.3.1193

PubMed ID

  • 10640730

Additional Document Info

volume

  • 164

issue

  • 3