An Analysis of Regulatory T-Cell and Th-17 Cell Dynamics during Cytomegalovirus Replication in Solid Organ Transplant Recipients

Autor: Leticia E. Wilson, Luiz Augusto Ferreira Lisboa, Adrian Egli, Luis G. Hidalgo, Moacyr Silva, Daire O'Shea, Deepali Kumar, Aliyah Baluch, Atul Humar
Rok vydání: 2012
Předmět:
Cytomegalovirus Infection
CD4-Positive T-Lymphocytes
Male
Viral Diseases
Time Factors
Cytomegalovirus
Transplants
lcsh:Medicine
Adaptive Immunity
CD8-Positive T-Lymphocytes
Virus Replication
T-Lymphocytes
Regulatory
Cohort Studies
Recurrence
Prospective Studies
IL-2 receptor
lcsh:Science
Multidisciplinary
T Cells
virus diseases
FOXP3
hemic and immune systems
Middle Aged
Viral Load
Infectious Diseases
medicine.anatomical_structure
Medicine
Female
Viral load
Research Article
Adult
Clinical Research Design
Regulatory T cell
Immune Cells
Immunology
chemical and pharmacologic phenomena
Context (language use)
Viremia
Biology
Immune Suppression
Species Specificity
medicine
Humans
Immunity to Infections
Aged
Transplantation
lcsh:R
Immunity
Immunologic Subspecialties
medicine.disease
Kinetics
Th17 Cells
Clinical Immunology
lcsh:Q
Biomarkers
CD8
Zdroj: PLoS ONE
PLoS ONE, Vol 7, Iss 11, p e43937 (2012)
ISSN: 1932-6203
Popis: BACKGROUND: CMV-specific T-cells are crucial to control CMV-replication post-transplant. Regulatory T-cells (T-regs) are associated with a tolerant immune state and may contribute to CMV-replication. However, T-cell subsets such as T-regs and IL-17 producing T-cells (Th-17) are not well studied in this context. We explored T-regs and Th-17 frequencies during CMV-replication after transplantation. METHODS: We prospectively evaluated 30 transplant patients with CMV-viremia. We quantified CMV-specific CD4(+) and CD8(+) T-cells, T-regs (CD4(+)CD25(+)FoxP3(+)) and Th-17 frequencies using flow-cytometry and followed patients requiring anti-viral treatment. Two subsets were compared: anti-viral treatment requirement (n = 20) vs. spontaneous clearance of viremia (n = 10). RESULTS: Higher initial CMV-specific CD4(+) T-cells and lower T-regs were observed in patients with spontaneous clearance (p = 0.043; p = 0.021 respectively). Using a ratio of CMV-specific CD4(+) T-cells to T-regs allowed prediction of viral clearance with 80% sensitivity and 90% specificity (p = 0.001). One month after stop of treatment, the same correlation was observed in patients protected from CMV-relapse. The ratio of CMV-specific CD4(+) T-cells to T-regs allowed prediction of relapse with 85% sensitivity and 86% specificity (p = 0.004). Th-17 responses were not correlated with virologic outcomes. CONCLUSIONS: This study provides novel insights into T-regs and Th-17 subpopulations during CMV-replication after transplantation. These preliminary data suggest that measurement of CMV-specific CD4(+) T-cells together with T-regs has value in predicting spontaneous clearance of viremia and relapse.
Databáze: OpenAIRE
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