An analysis of regulatory T-cell and Th-17 cell dynamics during cytomegalovirus replication in solid organ transplant recipients.
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.
Alberta Transplant Institute and Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada. aegli@ualberta.ca
Adrian
A
Egli
Moacyr
M
Silva
Daire
D
O'Shea
Leticia E
LE
Wilson
Aliyah
A
Baluch
Luiz F
LF
Lisboa
Luis G
LG
Hidalgo
Deepali
D
Kumar
Atul
A
Humar
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D003587:Cytomegalovirus / Q000276:immunology / Q000502:physiology*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D013045:Species Specificity; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000821:virology*; D058504:Th17 Cells / Q000276:immunology* / Q000821:virology*; D013997:Time Factors; D019737:Transplants / Q000821:virology*; D019562:Viral Load / Q000276:immunology; D014766:Viremia / Q000276:immunology; D014779:Virus Replication / Q000276:immunology*
D015415:Biomarkers