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J Infect Dis. 2015 Aug 1;212(3):484-94. doi: 10.1093/infdis/jiv071. Epub 2015 Feb 5.

Functional Exhaustion Limits CD4+ and CD8+ T-Cell Responses to Congenital Cytomegalovirus Infection.

Author information

1
Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi.
2
Department of Neonatology.
3
ImmuneHealth, Gosselies, Belgium.
4
Department of Obstetrics and Gynecology, Hôpital Saint-Pierre.
5
Department of Virology.
6
Hôpital Pitié-Salpêtrière, Université Pierre et Marie Curie-Paris 6, France.
7
Department of Obstetrics and Gynecology, Hôpital Erasme, Brussels.
8
Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi ImmuneHealth, Gosselies, Belgium.

Abstract

BACKGROUND:

Cytomegalovirus (CMV) infection during fetal life causes severe symptoms and is associated with prolonged viral excretion. Previous studies reported low CD4(+) T-cell responses to CMV infection in early life, contrasting with large responses of effector CD8(+) T cells. The mechanisms underlying the defective CD4(+) T-cell responses and the possible dissociation with CD8(+) T-cell responses have not been clarified.

METHODS:

The magnitude and the quality of the fetal CD8(+) and CD4(+) T-cell responses to CMV infection were compared to those of adults with primary or chronic infection.

RESULTS:

In utero CMV infection induced oligoclonal expansions of fetal CD4(+) and CD8(+) T lymphocytes expressing a T-helper type 1 or Tc1 effector phenotype similar to that of adult CMV-specific cells. However, the effector cytokine responses and the polyfunctionality of newborn CD4(+) and CD8(+) T cells were markedly lower than those of adult cells. This reduced functionality was associated with a higher expression of the programmed death 1 inhibitory receptor, and blockade of this receptor increased newborn T-cell responses.

CONCLUSIONS:

Functional exhaustion limits effector CD4(+) and CD8(+) T-lymphocyte responses to CMV during fetal life.

KEYWORDS:

CD4 T cell; CD8 T cell; congenital infection; cytomegalovirus; exhaustion; fetus

PMID:
25657256
DOI:
10.1093/infdis/jiv071
[Indexed for MEDLINE]

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