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Immunization of newborns against viral infections may be hampered by ineffective CD8(+) T cell responses. To characterize the function of CD8(+) T lymphocytes in early life, we studied newborns with congenital human cytomegalovirus (HCMV) infection. We demonstrate that HCMV infection in utero leads to the expansion and the differentiation of mature HCMV-specific CD8(+) T cells, which have similar characteristics to those detected in adults. High frequencies of HCMV-specific CD8(+) T cells were detected by ex vivo tetramer staining as early as after 28 weeks of gestation. During the acute phase of infection, these cells had an early differentiation phenotype (CD28(-)CD27(+)CD45RO(+), perforin(low)), and they acquired a late differentiation phenotype (CD28(-)CD27(-)CD45RA(+), perforin(high)) during the course of the infection. The differentiated cells showed potent perforin-dependent cytolytic activity and produced antiviral cytokines. The finding of a mature and functional CD8(+) T cell response to HCMV suggests that the machinery required to prime such responses is in place during fetal life and could be used to immunize newborns against viral pathogens.

Original publication

DOI

10.1172/JCI17470

Type

Journal article

Journal

J Clin Invest

Publication Date

06/2003

Volume

111

Pages

1747 - 1755

Keywords

Antigens, CD27, Antigens, CD28, Antigens, CD45, CD8-Positive T-Lymphocytes, Cell Differentiation, Cytomegalovirus Infections, Female, Fetus, Flow Cytometry, Histocompatibility Antigens, Humans, Immunologic Memory, Immunophenotyping, Infant, Newborn, Membrane Glycoproteins, Peptides, Perforin, Phenotype, Polymerase Chain Reaction, Pore Forming Cytotoxic Proteins, Pregnancy, Time Factors