Mature CD8(+) T lymphocyte response to viral infection during fetal life

Arnaud Marchant; Victor Appay; Marianne Van Der Sande; Nicolas Dulphy; Corinne Liesnard; Michael Kidd; Steve Kaye; Olubukola Ojuola; Geraldine M A Gillespie; Ana L Vargas Cuero; Vincenzo Cerundolo; Margaret Callan; Keith P W J McAdam; Sarah L Rowland-Jones; Catherine Donner; Andrew J McMichael; Hilton C Whittle

doi:10.1172/JCI17470

Mature CD8(+) T lymphocyte response to viral infection during fetal life

Arnaud Marchant, Victor Appay, Marianne Van Der Sande, Nicolas Dulphy, Corinne Liesnard, Michael Kidd, Steve Kaye, Olubukola Ojuola, Geraldine M A Gillespie, Ana L Vargas Cuero, Vincenzo Cerundolo, Margaret Callan, Keith P W J McAdam, Sarah L Rowland-Jones, Catherine Donner, Andrew J McMichael, Hilton C Whittle

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	1747-55
Number of pages	9
Journal	Journal of Clinical Investigation
Volume	111
Issue number	11
DOIs	https://doi.org/10.1172/JCI17470
Publication status	Published - Jun 2003

Keywords

CD28 Antigens
CD8-Positive T-Lymphocytes
Cell Differentiation
Cytomegalovirus Infections
Female
Fetus
Flow Cytometry
Histocompatibility Antigens
Humans
Immunologic Memory
Immunophenotyping
Infant, Newborn
Leukocyte Common Antigens
Membrane Glycoproteins
Peptides
Perforin
Phenotype
Polymerase Chain Reaction
Pore Forming Cytotoxic Proteins
Pregnancy
Time Factors
Tumor Necrosis Factor Receptor Superfamily, Member 7
Journal Article
Research Support, Non-U.S. Gov't

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10.1172/JCI17470

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Marchant, A., Appay, V., Van Der Sande, M., Dulphy, N., Liesnard, C., Kidd, M., Kaye, S., Ojuola, O., Gillespie, G. M. A., Vargas Cuero, A. L., Cerundolo, V., Callan, M., McAdam, K. P. W. J., Rowland-Jones, S. L., Donner, C., McMichael, A. J., & Whittle, H. C. (2003). Mature CD8(+) T lymphocyte response to viral infection during fetal life. Journal of Clinical Investigation, 111(11), 1747-55. https://doi.org/10.1172/JCI17470

@article{09f337a93014450f87de0130e455b065,

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.",

keywords = "CD28 Antigens, CD8-Positive T-Lymphocytes, Cell Differentiation, Cytomegalovirus Infections, Female, Fetus, Flow Cytometry, Histocompatibility Antigens, Humans, Immunologic Memory, Immunophenotyping, Infant, Newborn, Leukocyte Common Antigens, Membrane Glycoproteins, Peptides, Perforin, Phenotype, Polymerase Chain Reaction, Pore Forming Cytotoxic Proteins, Pregnancy, Time Factors, Tumor Necrosis Factor Receptor Superfamily, Member 7, Journal Article, Research Support, Non-U.S. Gov't",

author = "Arnaud Marchant and Victor Appay and {Van Der Sande}, Marianne and Nicolas Dulphy and Corinne Liesnard and Michael Kidd and Steve Kaye and Olubukola Ojuola and Gillespie, {Geraldine M A} and {Vargas Cuero}, {Ana L} and Vincenzo Cerundolo and Margaret Callan and McAdam, {Keith P W J} and Rowland-Jones, {Sarah L} and Catherine Donner and McMichael, {Andrew J} and Whittle, {Hilton C}",

year = "2003",

month = jun,

doi = "10.1172/JCI17470",

language = "English",

volume = "111",

pages = "1747--55",

journal = "Journal of Clinical Investigation",

issn = "0021-9738",

publisher = "American Society for Clinical Investigation",

number = "11",

}

Marchant, A, Appay, V, Van Der Sande, M, Dulphy, N, Liesnard, C, Kidd, M, Kaye, S, Ojuola, O, Gillespie, GMA, Vargas Cuero, AL, Cerundolo, V, Callan, M, McAdam, KPWJ, Rowland-Jones, SL, Donner, C, McMichael, AJ & Whittle, HC 2003, 'Mature CD8(+) T lymphocyte response to viral infection during fetal life', Journal of Clinical Investigation, vol. 111, no. 11, pp. 1747-55. https://doi.org/10.1172/JCI17470

TY - JOUR

T1 - Mature CD8(+) T lymphocyte response to viral infection during fetal life

AU - Marchant, Arnaud

AU - Appay, Victor

AU - Van Der Sande, Marianne

AU - Dulphy, Nicolas

AU - Liesnard, Corinne

AU - Kidd, Michael

AU - Kaye, Steve

AU - Ojuola, Olubukola

AU - Gillespie, Geraldine M A

AU - Vargas Cuero, Ana L

AU - Cerundolo, Vincenzo

AU - Callan, Margaret

AU - McAdam, Keith P W J

AU - Rowland-Jones, Sarah L

AU - Donner, Catherine

AU - McMichael, Andrew J

AU - Whittle, Hilton C

PY - 2003/6

Y1 - 2003/6

N2 - 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.

AB - 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.

KW - CD28 Antigens

KW - CD8-Positive T-Lymphocytes

KW - Cell Differentiation

KW - Cytomegalovirus Infections

KW - Female

KW - Fetus

KW - Flow Cytometry

KW - Histocompatibility Antigens

KW - Humans

KW - Immunologic Memory

KW - Immunophenotyping

KW - Infant, Newborn

KW - Leukocyte Common Antigens

KW - Membrane Glycoproteins

KW - Peptides

KW - Perforin

KW - Phenotype

KW - Polymerase Chain Reaction

KW - Pore Forming Cytotoxic Proteins

KW - Pregnancy

KW - Time Factors

KW - Tumor Necrosis Factor Receptor Superfamily, Member 7

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1172/JCI17470

DO - 10.1172/JCI17470

M3 - Article

C2 - 12782677

SN - 0021-9738

VL - 111

SP - 1747

EP - 1755

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

IS - 11

ER -

Mature CD8(+) T lymphocyte response to viral infection during fetal life

Abstract

Keywords

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