Allospecific CD154+ T-cytotoxic memory cells identify recipients experiencing acute cellular rejection after renal transplantation

Transplantation. 2011 Aug 27;92(4):433-8. doi: 10.1097/TP.0b013e318225276d.

Abstract

Background: The novel, recently described allo (antigen)-specific CD154+T cells were evaluated for their association with acute cellular rejection (ACR) in 43 adult renal transplant recipients receiving steroid-free tacrolimus after alemtuzumab induction.

Methods: Single blood samples corresponding to "for cause" allograft biopsies were assayed for CD154+naive or memory T-helper or T-cytotoxic cells in 16-hr mixed leukocyte reaction.

Results: Intra- and interassay variation was less than 10% for a variety of conditions. In logistic regression, leave-one-out cross-validation, and receiver-operating characteristic analyses, the rejection-risk threshold of allospecific CD154+T-cytotoxic memory cells (TcMs) associated best with biopsy-proven ACR with a sensitivity/specificity of 88% in 32 of 43 subjects. Sensitivity/specificity of 100%/88% was replicated in blinded prediction in the remaining 11 subjects. Allospecific CD154+TcM correlated inversely with CTLA4+TcM (Spearman r=-0.358, P=0.029) and increased significantly with increasing histological severity of ACR (P=2.99E-05, Kruskall-Wallis).

Conclusions: The strong association between ACR and allospecific CD154+TcM may be useful in minimizing protocol biopsies among recipients at reduced rejection risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • CD40 Ligand / metabolism*
  • Female
  • Graft Rejection / etiology*
  • Graft Rejection / immunology*
  • Graft Rejection / pathology
  • Humans
  • Immunologic Memory
  • Immunosuppressive Agents / therapeutic use
  • Isoantigens
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / immunology*
  • Kidney Transplantation / pathology
  • Male
  • Middle Aged
  • Risk Factors
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • Tacrolimus / therapeutic use
  • Young Adult

Substances

  • Immunosuppressive Agents
  • Isoantigens
  • CD40 Ligand
  • Tacrolimus