Phenotype and specificity of T cells in primary human cytomegalovirus infection during pregnancy

IL-7Rpos long-term memory phenotype is associated with protection from vertical transmission

Federico Mele, Chiara Fornara, David Jarrossay, Milena Furione, Alessia Arossa, Arsenio Spinillo, Antonio Lanzavecchia, Giuseppe Gerna, Federica Sallusto, Daniele Lilleri

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Congenital human cytomegalovirus (HCMV) infection is the major cause of birth defects and a precise definition of the HCMV-specific T-cell response in primary infection may help define reliable correlates of immune protection during pregnancy. In this study, a high throughput method was used to define the frequency of CD4+ and CD8+ T cells specific for four HCMV proteins in the naïve compartment of seronegative subjects and the effector/memory compartments of subjects with primary/remote HCMV infection. The naïve repertoire displayed comparable frequencies of T cells that were reactive with HCMV structural (pp65, gB and the pentamer gHgLpUL128L) and non-structural (IE-1) proteins. Whereas, following natural infection, the majority of effector/memory CD4+ and CD8+ T cells recognized either gB or IE-1, respectively, and pp65. The pattern of T cell reactivity was comparable at early and late stages of infection and in pregnant women with primary HCMV infection transmitting or not transmitting the virus to the fetus. At an early stage of primary infection, about 50% of HCMV-reactive CD4+ T cells were long-term IL-7Rpos memory cells, while 6–12 months later, the frequency of these cells increased to 70%, approaching 100% in remote infections. In contrast, only 10–20% of HCMV-specific CD8+ T cells were long-term memory cells up to 12 months after infection onset, thereafter increasing to 70% in remote infections. Interestingly, a significantly higher frequency of HCMV-specific CD4+ T cells with a long-term IL-7Rpos memory phenotype was observed in non-transmitting compared to transmitting women. These findings indicate that immunodomi-nance in HCMV infection is not predetermined in the naïve compartment, but is the result of virus-host interactions and suggest that prompt control of HCMV infection in pregnancy is associated with the rapid development of long-term IL-7Rpos memory HCMV-specific CD4+ T cells and a low risk of virus transmission to the fetus.

Original languageEnglish
Article numbere0187731
JournalPLoS One
Volume12
Issue number11
DOIs
Publication statusPublished - Nov 1 2017

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T-Cell Antigen Receptor Specificity
Human herpesvirus 5
T-cells
Long-Term Memory
Cytomegalovirus Infections
T-lymphocytes
pregnancy
Phenotype
phenotype
Data storage equipment
Pregnancy
Cytomegalovirus
T-Lymphocytes
Viruses
Infection
infection
fetus
Cytomegalovirus infections
Fetus
viruses

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Phenotype and specificity of T cells in primary human cytomegalovirus infection during pregnancy : IL-7Rpos long-term memory phenotype is associated with protection from vertical transmission. / Mele, Federico; Fornara, Chiara; Jarrossay, David; Furione, Milena; Arossa, Alessia; Spinillo, Arsenio; Lanzavecchia, Antonio; Gerna, Giuseppe; Sallusto, Federica; Lilleri, Daniele.

In: PLoS One, Vol. 12, No. 11, e0187731, 01.11.2017.

Research output: Contribution to journalArticle

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abstract = "Congenital human cytomegalovirus (HCMV) infection is the major cause of birth defects and a precise definition of the HCMV-specific T-cell response in primary infection may help define reliable correlates of immune protection during pregnancy. In this study, a high throughput method was used to define the frequency of CD4+ and CD8+ T cells specific for four HCMV proteins in the na{\"i}ve compartment of seronegative subjects and the effector/memory compartments of subjects with primary/remote HCMV infection. The na{\"i}ve repertoire displayed comparable frequencies of T cells that were reactive with HCMV structural (pp65, gB and the pentamer gHgLpUL128L) and non-structural (IE-1) proteins. Whereas, following natural infection, the majority of effector/memory CD4+ and CD8+ T cells recognized either gB or IE-1, respectively, and pp65. The pattern of T cell reactivity was comparable at early and late stages of infection and in pregnant women with primary HCMV infection transmitting or not transmitting the virus to the fetus. At an early stage of primary infection, about 50{\%} of HCMV-reactive CD4+ T cells were long-term IL-7Rpos memory cells, while 6–12 months later, the frequency of these cells increased to 70{\%}, approaching 100{\%} in remote infections. In contrast, only 10–20{\%} of HCMV-specific CD8+ T cells were long-term memory cells up to 12 months after infection onset, thereafter increasing to 70{\%} in remote infections. Interestingly, a significantly higher frequency of HCMV-specific CD4+ T cells with a long-term IL-7Rpos memory phenotype was observed in non-transmitting compared to transmitting women. These findings indicate that immunodomi-nance in HCMV infection is not predetermined in the na{\"i}ve compartment, but is the result of virus-host interactions and suggest that prompt control of HCMV infection in pregnancy is associated with the rapid development of long-term IL-7Rpos memory HCMV-specific CD4+ T cells and a low risk of virus transmission to the fetus.",
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AU - Furione, Milena

AU - Arossa, Alessia

AU - Spinillo, Arsenio

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