Role of regulated upon activation normal T-cell expressed and secreted in a model of retransplantation acute rejection mediated by alloreactive memory CD4+ T cells

Transplant Proc. 2013 Mar;45(2):546-51. doi: 10.1016/j.transproceed.2012.11.005.

Abstract

Background: It is unknown what role Regulated Upon Activation Normal T-Cell Exposed and Secreted may play in retransplantation or T-cell memory-transfer models. The experiment observed the influence of the chemokine RANTES in a mouse model of acute cardiac allograft rejection induced by adoptive transfer of alloreactive CD4(+) memory T (Tm) cells.

Methods: Alloreactive CD4(+) Tm cells from spleens of skin-grafted C57BL/6 were adoptively transferred to naïve C57BL/6 recipients prior to heterotopic heart transplantation. We measured the median survival time of cardiac grafts and performed some tests.

Results: Spleens from skin-grafted C57BL/6 contained 26.83% CD4(+) Tm cells. The median graft survival time of heterotopic heart transplantations (n = 6) was 5.17 ± 0.17 days for hosts receiving CD4(+) Tm cells compared with 7.76 ± 0.21 days among controls (n = 6; P < .001). The mean rejection activity in histological sections of cardiac allografts at day 5 postgrafting was 3.92 ± 0.08 in the CD4(+) Tm cell recipient group (n = 6) compared with 2.67 ± 0.14 in the controls (n = 6; P < .001). Gene expression of Ccl5, interferon (IFN)-γ and interleukin2 was significantly higher among CD4(+) Tm recipients compared with controls. Serum concentrations of RANTES and IFN-γ were higher in the heterotopic heart transplantation group receiving CD4(+) Tm compared with controls.

Conclusions: Alloreactive CD4(+) Tm cells contribute to increased expression and secretion of RANTES, and to the Tm and other inflammatory cells migration into the graft.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adoptive Transfer
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / transplantation
  • Cell Movement
  • Chemokine CCL5 / blood
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / metabolism*
  • Graft Rejection / blood
  • Graft Rejection / immunology*
  • Graft Rejection / pathology
  • Graft Survival*
  • Heart Transplantation / adverse effects
  • Heart Transplantation / immunology*
  • Immunologic Memory*
  • Interferon-gamma / blood
  • Interferon-gamma / genetics
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Phenotype
  • Skin Transplantation / immunology
  • Time Factors

Substances

  • Ccl5 protein, mouse
  • Chemokine CCL5
  • Interleukin-2
  • Interferon-gamma