The role of CC chemokine receptor 5 (CCR5) in islet allograft rejection

Diabetes. 2002 Aug;51(8):2489-95. doi: 10.2337/diabetes.51.8.2489.

Abstract

Chemokines are important regulators in the development, differentiation, and anatomic location of leukocytes. CC chemokine receptor 5 (CCR5) is expressed preferentially by CD4(+) T helper 1 (Th1) cells. We sought to determine the role of CCR5 in islet allograft rejection in a streptozotocin-induced diabetic mouse model. BALB/c islet allografts transplanted into CCR5(-/-) (C57BL/6) recipients survived significantly longer (mean survival time, 38 +/- 8 days) compared with those transplanted into wild-type control mice (10 +/- 2 days; P < 0.0001). Twenty percent of islet allografts in CCR5(-/-) animals without other treatment survived >90 days. In CCR5(-/-) mice, intragraft mRNA expression of interleukin-4 and -5 was increased, whereas that of interferon-gamma was decreased, corresponding to a Th2 pattern of T-cell activation in the target tissues compared with a Th1 pattern observed in controls. A similar Th2 response pattern was also observed in the periphery (splenocytes responding to donor cells) by enzyme-linked immunosorbent spot assay. We conclude that CCR5 plays an important role in orchestrating the Th1 immune response leading to islet allograft rejection. Targeting this chemokine receptor, therefore, may provide a clinically useful strategy to prevent islet allograft rejection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokines / genetics
  • Cytokines / genetics
  • Graft Rejection / immunology
  • Graft Rejection / pathology*
  • Graft Survival / immunology*
  • Histocompatibility Testing
  • Islets of Langerhans Transplantation / immunology
  • Islets of Langerhans Transplantation / pathology*
  • Lymphocyte Culture Test, Mixed
  • Mice
  • Mice, Knockout
  • Receptors, CCR5 / deficiency
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / immunology*
  • Receptors, Chemokine / genetics
  • T-Lymphocytes / immunology*
  • Th1 Cells / immunology
  • Transplantation, Homologous
  • Transplantation, Isogeneic

Substances

  • Chemokines
  • Cytokines
  • Receptors, CCR5
  • Receptors, Chemokine