Development of Human Cytomegalovirus–Specific T Cell Immunity during Primary Infection of Pregnant Women and Its Correlation with Virus Transmission to the Fetus

Lilleri, Daniele; Fornara, Chiara; Furione, Milena; Zavattoni, Maurizio; Revello, Maria Grazia; Gerna, Giuseppe

doi:10.1086/512245

Cited by 111 publications

(93 citation statements)

References 34 publications

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“…Different techniques have been applied for monitoring of CD8 þ and/or CD4 þ CMV-specific T-cells, mainly by HLArestricted tetramers containing immunodominant peptides from CMV or measurement of peptide-specific intracellular cytokine staining. [39][40][41][42] Unfortunately, such tests are not available at most transplant centres.…”

Section: Discussionmentioning

confidence: 99%

Cytomegalovirus infection and disease after reduced intensity conditioning allogeneic stem cell transplantation: single-centre experience

Piñana

Martino

Barba

et al. 2009

Bone Marrow Transplant

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The aim of this study was to analyse the incidence and risk factors for cytomegalovirus infection (CMV-I) and disease (CMV-D) after a reduced intensity conditioning allogeneic hematopoietic stem cell transplantation (alloHSCT-RIC). We included 186 consecutive alloHSCT-RIC adult patients at risk for CMV reactivation (patient and/or donor CMV seropositivity). Conditioning regimen was based on fludarabine plus an alkylating agent. For guiding pre-emptive anti-CMV therapy, Pp65 Antigenemia (pp65Ag) (n ¼ 116) or quantitative polymerase chain reaction (quantPCR) (n ¼ 70) were used. The 2-year incidence of CMV-I and/or CMV-D was 36% (11% for CMV-D). Of note, 12/14 (86%) episodes of CMV-D in the pp65Ag group had lung involvement compared with only 3/ 15 (20%) in the quantPCR group (P ¼ 0.01). Importantly, the number of patients who developed CMV pneumonia with prior negative screening tests was unusually high (67% overall). Multivariate analysis of risk factors for CMV-D identified two risk factors: (i) steroid therapy for moderateto-severe graft-vs-host disease (GVHD) (hazard ratio 4.7, P ¼ 0.02); and (ii) alternative donors (non-HLA-identical siblings) [hazard ratio 2.7, P ¼ 0.002]. Our findings suggest that CMV is still a major concern in alloHSCT-RIC. Variables associated with poor anti-CMV T-cell recovery (that is, GVHD and donor type) are helpful in identifying patients at higher risk for CMV-D in the alloHSCT-RIC setting.

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Section: Discussionmentioning

confidence: 99%

Cytomegalovirus infection and disease after reduced intensity conditioning allogeneic stem cell transplantation: single-centre experience

Piñana

Martino

Barba

et al. 2009

Bone Marrow Transplant

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“…21,23,24 Monitoring of CD8 and/or CD4 CMV-specific T cells has, therefore, been studied, and different techniques can be applied including detection by tetramers containing immunodominant peptides from CMV or measurement of peptide-specific intracellular cytokine staining. [25][26][27][28] Techniques for collecting and expanding CMV-specific T cells including the use of peptide-pulsed dendritic cells, selection by tetramer technology or vaccination with peptide-pulsed dendritic cells have been developed, and several centers are testing these strategies in clinical trials. [28][29][30][31][32] …”

mentioning

confidence: 99%

CMV infections after hematopoietic stem cell transplantation

Ljungman

2008

Bone Marrow Transplant

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“…infection in many individuals no overt symptoms are observed, CMV came to medical attention due to its significant morbidity and mortality associated with congenital infec- In pregnant women following natural primary infection, viral replication is controlled by the emergence of antigen-specific CD4 + , CD8 + and CD45RA + effector memory T-cells 7,8 . Lower frequencies of CMV-specific CD4 + T-cells and CD45RA + cells in mothers following primary infection is known to be associated with virus transmission to the fetus 9,10 .…”

Section: Although Following Primary Human Cytomegalovirus (Cmv)mentioning

confidence: 99%

Vaccination for cytomegalovirus: when, where and how

Dasari

Khanna

2015

Microbiol. Aust.

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Although following primary human cytomegalovirus (CMV)infection in many individuals no overt symptoms are observed, CMV came to medical attention due to its significant morbidity and mortality associated with congenital infec- In pregnant women following natural primary infection, viral replication is controlled by the emergence of antigen-specific CD4 + , CD8 + and CD45RA + effector memory T-cells 7,8 . Lower frequencies of CMV-specific CD4 + T-cells and CD45RA + cells in mothers following primary infection is known to be associated with virus transmission to the fetus 9,10 . Based on these observations it can be hypothesised that emergence of higher frequencies of CMV-specific CD4 + , CD8 + and CD45RA + effector memory T-cells may be associated with control of viremia and prevention of transplacental transmission. Therefore, an effective CMV vaccine specially designed to induce CMV-specific CD4 + , CD8 + and CD45RA + effector memory T-cells in women of reproductive age could potentially decrease CMV transmission to the fetus and vaccination of infants, toddlers and adolescents could reduce the duration of viral shedding, which may reduce child-to-mother transmission.Clinical evaluation of active and passive immunisation strategies against CMV in the context of congenital CMV Live attenuated virus vaccinesThe initial CMV vaccine trials based on an attenuated form of CMV isolates Towne and AD169 11,12 induced humoral and cellular Under the Microscope

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Development of Human Cytomegalovirus–Specific T Cell Immunity during Primary Infection of Pregnant Women and Its Correlation with Virus Transmission to the Fetus

Abstract: The development of adaptive T cell immunity after primary HCMV infection appears to be a complex and slow process until a memory T cell response develops. The T cell immune response appears to influence vertical HCMV transmission.

Cited by 111 publications

References 34 publications

Cytomegalovirus infection and disease after reduced intensity conditioning allogeneic stem cell transplantation: single-centre experience

Cytomegalovirus infection and disease after reduced intensity conditioning allogeneic stem cell transplantation: single-centre experience

CMV infections after hematopoietic stem cell transplantation

Vaccination for cytomegalovirus: when, where and how

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