PD-1 analysis on CD28(-) CD27(-) CD4 T cells allows stimulation-independent assessment of CMV viremic episodes in transplant recipients.

Abstract

Expression of the inhibitory receptor programmed death 1 (PD-1) on cytomegalovirus (CMV)-specific CD4 T cells defines a phenotype associated with CMV viremia in transplant recipients. Moreover, CD28(-) CD27(-) double negativity is known as a typical phenotype of CMV-specific CD4 T cells. Therefore, the co-expression of inhibitory receptors on CD28(-) CD27(-) CD4 T cells was assessed as a rapid, stimulation-independent parameter for monitoring CMV complications after transplantation. Ninety-three controls, 67 hemodialysis patients and 81 renal transplant recipients were recruited in a cross-sectional and longitudinal manner. CMV-specific CD4 T cell levels quantified after stimulation were compared to levels of CD28(-) CD27(-) CD4 T cells. PD-1 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) expression on CD28(-) CD27(-) CD4 T cells were related to viremia. A percentage of ≥0.44% CD28(-) CD27(-) CD4 T cells defined CMV seropositivity (93.3% sensitivity, 97.1% specificity), and their frequencies correlated strongly with CMV-specific CD4 T cell levels after stimulation (r = 0.73, p < 0.0001). Highest PD-1 expression levels on CD28(-) CD27(-) CD4 T cells were observed in patients with primary CMV viremia and reactivation (p < 0.0001), whereas CTLA-4 expression was only elevated during primary CMV viremia (p < 0.05). Longitudinal analysis showed a significant increase in PD-1 expression in relation to viremia (p < 0.001), whereas changes in nonviremic patients were nonsignificant. In conclusion, increased PD-1 expression on CD28(-) CD27(-) CD4 T cells correlates with CMV viremia in transplant recipients and may serve as a specific, stimulation-independent parameter to guide duration of antiviral therapy.

• Authors: J Dirks, H Tas, T Schmidt, S Kirsch, B C Gärtner, U Sester, M Sester
• Journal: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (Am J Transplant) Vol. 13 Issue 12 Pg. 3132-41 (Dec 2013) ISSN: 1600-6143 [Electronic] United States
• PMID: 24148296 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Chemical References

• Antiviral Agents
• CD28 Antigens
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor
• Tumor Necrosis Factor Receptor Superfamily, Member 7

Topics

• Adult
• Antiviral Agents (chemistry)
• CD28 Antigens (metabolism)
• CD4-Positive T-Lymphocytes (cytology)
• Case-Control Studies
• Cross-Sectional Studies
• Cytomegalovirus
• Cytomegalovirus Infections (complications)
• Flow Cytometry
• Humans
• Kidney Transplantation
• Middle Aged
• Phenotype
• Postoperative Complications
• Programmed Cell Death 1 Receptor (metabolism)
• Renal Dialysis
• Renal Insufficiency (blood, complications, therapy)
• Sensitivity and Specificity
• Tumor Necrosis Factor Receptor Superfamily, Member 7 (metabolism)
• Viremia (complications)