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Antiviral Res. 2016 Aug;132:244-51. doi: 10.1016/j.antiviral.2016.06.012. Epub 2016 Jul 1.

Prevention strategies differentially modulate the impact of cytomegalovirus replication on CD8(+) T-cell differentiation in high-risk solid organ transplant patients.

Author information

1
Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/Reina Sofia University Hospital/University of Cordoba, Cordoba, Spain.
2
Instituto de Biomedicina de Sevilla (IBiS), Virgen del Rocío University Hospital/ CSIC/University of Sevilla, Unit of Infectious Diseases, Microbiology and Preventive Medicine, Sevilla, Spain.
3
Infectious Diseases Unit, Cruces University Hospital, Bilbao, Spain.
4
Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/Reina Sofia University Hospital/University of Cordoba, Cordoba, Spain; Department of Microbiology, Reina Sofia University Hospital, Cordoba, Spain.
5
Department of Nephrology, Cruces University Hospital, Bilbao, Spain.
6
Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/Reina Sofia University Hospital/University of Cordoba, Cordoba, Spain; Department of Immunology, Reina Sofia University Hospital, Cordoba, Spain. Electronic address: rsolana@uco.es.
7
Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/Reina Sofia University Hospital/University of Cordoba, Cordoba, Spain; Infectious Diseases Unit, Reina Sofia University Hospital, Cordoba, Spain.

Abstract

The present study aimed to determine whether antiviral prevention strategies against cytomegalovirus (CMV) infection used in high-risk D+R- solid organ transplanted patients can modulate the impact of CMV replication on CD8(+) T-cell differentiation. The different CD8(+) T-cell subpopulations were measured at a single point when at least one year had elapsed since transplantation. A total of 68 D+R- patients were included, of which 33 underwent pre-emptive therapy and 35 received prophylaxis. Multivariate analysis showed that CMV replication was associated with the expansion of CD28־ EMRA CD8(+) T cells in patients managed pre-emptively but not in patients under prophylaxis (21.4% vs. 3.6%). This finding is likely related to the higher frequency of CMV recurrence observed in patients under pre-emptive therapy compared to those under prophylaxis (75% vs. 14.3%; p < 0.001). In fact, multivariate analysis showed that having more than one replication episode was associated with a 17.2% increase (p = 0.001) in the percentage of CD28־ EMRA CD8(+) T cells compared to "no episode" and with a 10.9% increase with respect to "single episodes" (p = 0.025). Additionally, patients with IFNγ response to CMV (QuantiFERON-CMV Reactive) had a higher percentage of late-differentiated CD8(+) T cells than patients lacking this response. In summary, recurrent CMV replication in D+R- patients under pre-emptive therapy was associated with the expansion of CD28־ EMRA CD8(+) T cells, which might have a short-term beneficial effect related to the high functionality of this T-cell subpopulation. Nevertheless, we cannot rule out that this accumulation might have a long-term detrimental effect related to immunosenescence and inflammation.

KEYWORDS:

Antiviral prevention strategies; CMV replication; D+R- patients; Interferon-gamma; Late-differentiated CD8(+) T cells; Solid organ transplantation

PMID:
27378225
DOI:
10.1016/j.antiviral.2016.06.012
[Indexed for MEDLINE]

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