Allospecific CD154+ T-Cytotoxic Memory Cells Identify Recipients Experiencing Acute Cellular Rejection After Renal Transplantation.
Summary of "Allospecific CD154+ T-Cytotoxic Memory Cells Identify Recipients Experiencing Acute Cellular Rejection After Renal Transplantation."
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.
Affiliation
1 Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA. 2 Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA. 3 Hillman Center for Pediatric Tra
Journal Details
This article was published in the following journal.
Name: Transplantation
ISSN: 1534-6080
Pages: 433-8
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21747326
- DOI: http://dx.doi.org/10.1097/TP.0b013e318225276d
Medical and Biotech [MESH] Definitions
Cytotoxicity, Immunologic
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
Rosette Formation
The in vitro formation of clusters consisting of a cell (usually a lymphocyte) surrounded by antigenic cells or antigen-bearing particles (usually erythrocytes, which may or may not be coated with antibody or antibody and complement). The rosette-forming cell may be an antibody-forming cell, a memory cell, a T-cell, a cell bearing surface cytophilic antibodies, or a monocyte possessing Fc receptors. Rosette formation can be used to identify specific populations of these cells.
Interleukin-18
A cytokine which resembles IL-1 structurally and IL-12 functionally. It enhances the cytotoxic activity of NK CELLS and CYTOTOXIC T-LYMPHOCYTES, and appears to play a role both as neuroimmunomodulator and in the induction of mucosal immunity.
T-lymphocytes, Cytotoxic
Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.
Memory
Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory.
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