Abstract
Primary infection with cytomegalovirus (CMV) in immunocompetent hosts is accompanied with activation and differentiation of naive CD8+ T cells to effector/memory cells secreting interferon-γ (IFN-γ). Alteration of these responses during the perinatal period is suggested by a higher rate of CMV diseases in congenital infection. For addressing this issue, immunologic investigations were performed in 15 fetuses (22–36 wk of gestation) with documented congenital CMV infection. Results show that cellular immune responses can be detected as soon as the 22nd week of gestation (the youngest fetus analyzed). Compared with age-matched control subjects, infected fetuses evidence a dramatic increase in the percentages of activated and terminally differentiated CD8 T cells. Indeed, median percentages (interquartile range) of HLA-DR+ and of CD28−CD8+ T cells were 24% (19–34) and 38% (24–52), respectively in infected fetuses versus 3% (0–4) for each subset in control subjects. In addition, the percentages of T cells secreting IFN-γ after in vitro stimulation with phorbol myristate acetate and ionomycin was significantly higher in infected fetuses [10% (5–25)] than in healthy fetuses [0.8% (0.6–1.2)] with IFN-γ being mostly secreted by CD8+ T cells and to a lesser extend by CD4+ T cells. These cellular immune responses have clear similarities with responses previously reported in adults. Cellular immunity to CMV, however, might not be fully functional in fetuses. Indeed, the number of T cells capable of secreting IFN-γ is strikingly lower after in vitro stimulation with the CMV-specific antigen than after in vitro stimulation with phorbol myristate acetate/ionomycin that bypasses signaling through the T-cell receptor.
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Abbreviations
- CMV:
-
cytomegalovirus
- IFN-γ:
-
interferon-γ
- PMA:
-
phorbol myristate acetate
- Ca2+:
-
ionomycin
- PBMC:
-
peripheral-blood mononuclear cells
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Acknowledgements
The cooperation of all patients and control subjects is gratefully acknowledged. We thank Christophe Merlette, Catherine Martinet, and Valérie Broc for excellent technical assistance; Sandie Samb and Nadine Battery for typing the manuscript; and Corine Alberti for advice regarding statistical analysis.
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Elbou Ould, M., Luton, D., Yadini, M. et al. Cellular Immune Response of Fetuses to Cytomegalovirus. Pediatr Res 55, 280–286 (2004). https://doi.org/10.1203/01.PDR.0000104150.85437.FE
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DOI: https://doi.org/10.1203/01.PDR.0000104150.85437.FE
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