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Multicenter Study
. 2023 Feb 6;18(2):e0281341.
doi: 10.1371/journal.pone.0281341. eCollection 2023.

The role of the T-cell mediated immune response to Cytomegalovirus infection in intrauterine transmission

María Soriano-Ramos  1   2 , Estrella Esquivel-De la Fuente  2 , Eliseo Albert Vicent  3 , María de la Calle  4 , Fernando Baquero-Artigao  5 , Sara Domínguez-Rodríguez  2 , María Cabanes  6 , Enery Gómez-Montes  7 , Anna Goncé  8 , Marta Valdés-Bango  8 , Mª Carmen Viñuela-Benéitez  9 , Mar Muñoz-Chápuli Gutiérrez  9 , Jesús Saavedra-Lozano  10 , Irene Cuadrado Pérez  11 , Begoña Encinas  12 , Laura Castells Vilella  13 , María de la Serna Martínez  14 , Alfredo Tagarro  15 , Paula Rodríguez-Molino  5 , Estela Giménez Quiles  3 , Diana García Alcázar  7 , Antonio García Burguillo  16 , María Dolores Folgueira  17 , David Navarro  3 , Daniel Blázquez-Gamero  2   18 ; CYTRIC Study Group
Affiliations
Multicenter Study

The role of the T-cell mediated immune response to Cytomegalovirus infection in intrauterine transmission

María Soriano-Ramos et al. PLoS One. .

Abstract

Introduction: Prognostic markers for fetal transmission of Cytomegalovirus (CMV) infection during pregnancy are poorly understood. Maternal CMV-specific T-cell responses may help prevent fetal transmission and thus, we set out to assess whether this may be the case in pregnant women who develop a primary CMV infection.

Methods: A multicenter prospective study was carried out at 8 hospitals in Spain, from January 2017 to April 2020. Blood samples were collected from pregnant women at the time the primary CMV infection was diagnosed to assess the T-cell response. Quantitative analysis of interferon producing specific CMV-CD8+/CD4+ cells was performed by intracellular cytokine flow cytometry.

Results: In this study, 135 pregnant women with a suspected CMV infection were evaluated, 60 of whom had a primary CMV infection and samples available. Of these, 24 mothers transmitted the infection to the fetus and 36 did not. No association was found between the presence of specific CD4 or CD8 responses against CMV at the time maternal infection was diagnosed and the risk of fetal transmission. There was no transmission among women with an undetectable CMV viral load in blood at diagnosis.

Conclusions: In this cohort of pregnant women with a primary CMV infection, no association was found between the presence of a CMV T-cell response at the time of maternal infection and the risk of intrauterine transmission. A detectable CMV viral load in the maternal blood at diagnosis of the primary maternal infection may represent a relevant biomarker associated with fetal transmission.

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Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: DBG received fees from MSD as speaker in educational activities. None of the remaining authors have any conflict of interests to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Gating strategy for the enumeration of CMV-specific IFN-γ producing CD4+ and CD8+ T cells by Intracellular Cytokine Staining (ICS).
Total Lymphocyte/CD3+/CD8+ or Lymphocyte/CD3+/CD4+ events were gated and then analyzed for CD69+/IFN‐γ production. Positive (Phytohemaglutinin) and negative controls (DMSO) were used.
Fig 2
Fig 2. Patient flowchart.
Flowchart showing outcome of 135 pregnant women with suspected Cytomegalovirus infection. CMV indicates Cytomegalovirus.
Fig 3
Fig 3. T-cell mediated immune response.
Violin plot showing the lymphocyte count and the association of CMV-CD8+IFN-γ, and CMV-CD4+IFN-γ with transmission.
Fig 4
Fig 4. CMV-CD4+IFN-γ lymphocytes relation with time between infection to blood sampling.
Model showing the time interval from infection to blood sampling against the predicted probability of CMV intrauterine transmission in women presenting a positive CD4 response (% of CD8-g-IFN producers above 0.1 in red) or not (in blue).
Fig 5
Fig 5. Interaction time–effect of CMV-CD8+IFN-γ lymphocytes.
Model showing the time interval from infection to blood sampling against the predicted probability of CMV intrauterine transmission in women presenting a positive CD8 response (% of CD8-g-IFN producers above 0.1 in red) or not (in blue).
See this image and copyright information in PMC

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