Mature CD8(+) T lymphocyte response to viral infection during fetal life.
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.
Marchant
Arnaud
A
Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom. arnaud.marchant@btinternet.com
Appay
Victor
V
Van Der Sande
Marianne
M
Dulphy
Nicolas
N
Liesnard
Corinne
C
Kidd
Michael
M
Kaye
Steve
S
Ojuola
Olubukola
O
Gillespie
Geraldine M A
GM
Vargas Cuero
Ana L
AL
Cerundolo
Vincenzo
V
Callan
Margaret
M
McAdam
Keith P W J
KP
Rowland-Jones
Sarah L
SL
Donner
Catherine
C
McMichael
Andrew J
AJ
Whittle
Hilton
H
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
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