title: Mature CD8(+) T lymphocyte response to viral infection during fetal life.
abstract: 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.
authors.affiliation: Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom. arnaud.marchant@btinternet.com
authors.forename: Arnaud
authors.initials: A
authors.lastname: Marchant
authors.forename: Victor
authors.initials: V
authors.lastname: Appay
authors.forename: Marianne
authors.initials: M
authors.lastname: Van Der Sande
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dulphy
authors.forename: Corinne
authors.initials: C
authors.lastname: Liesnard
authors.forename: Michael
authors.initials: M
authors.lastname: Kidd
authors.forename: Steve
authors.initials: S
authors.lastname: Kaye
authors.forename: Olubukola
authors.initials: O
authors.lastname: Ojuola
authors.forename: Geraldine M A
authors.initials: GM
authors.lastname: Gillespie
authors.forename: Ana L
authors.initials: AL
authors.lastname: Vargas Cuero
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerundolo
authors.forename: Margaret
authors.initials: M
authors.lastname: Callan
authors.forename: Keith P W J
authors.initials: KP
authors.lastname: McAdam
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Rowland-Jones
authors.forename: Catherine
authors.initials: C
authors.lastname: Donner
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Hilton
authors.initials: H
authors.lastname: Whittle
mesh_terms: D018106:CD28 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000517:prevention & control; D005260:Female; D005333:Fetus / Q000276:immunology* / Q000821:virology*; D005434:Flow Cytometry; D006649:Histocompatibility Antigens / Q000737:chemistry; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D016130:Immunophenotyping; D007231:Infant, Newborn; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D010455:Peptides / Q000737:chemistry; D054353:Perforin; D010641:Phenotype; D016133:Polymerase Chain Reaction; D052899:Pore Forming Cytotoxic Proteins; D011247:Pregnancy; D013997:Time Factors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis
chemical_list: D018106:CD28 Antigens; D006649:Histocompatibility Antigens; D008562:Membrane Glycoproteins; D010455:Peptides; D052899:Pore Forming Cytotoxic Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D054353:Perforin; D017493:Leukocyte Common Antigens