ICOS+PD-1+CXCR3+ T follicular helper cells contribute to the generation of high-avidity antibodies following influenza vaccination

Bentebibel, Salah Eddine; Khurana, Surender; Schmitt, Nathalie; Kurup, Parvathi; Mueller, Cynthia; Obermoser, Gerlinde; Palucka, A. Karolina; Albrecht, Randy A.; García‐Sastre, Adolfo; Golding, Hana; Ueno, Hideki

doi:10.1038/srep26494

Cited by 151 publications

(162 citation statements)

References 25 publications

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“…Previous studies have reported the positive correlation between the number of GC B cells and Tfh cells [26, 27]. Further, in humans Tfh helper cells have been reported to contribute to the production of high affinity antibodies following influenza vaccination [28]. Thus, one approach to achieve higher quality antibody is provision of additional modulatory signals that promote Tfh, e.g.…”

Section: Discussionmentioning

confidence: 99%

Adjuvanting an inactivated influenza vaccine with conjugated R848 improves the level of antibody present at 6 months in a nonhuman primate neonate model

Holbrook

D’Agostino

Aycock

et al. 2017

Vaccine

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Generation of a potent antibody response that can be sustained over time is highly challenging in young infants. Our previous studies using a nursery-reared nonhuman primate model identified R848 conjugated to inactivated influenza virus as a highly immunogenic vaccine for neonates. Here we determined the effectiveness of this vaccine in mother-reared infants as well as its ability to promote improved responses at 6 months compared to vaccination in the absence of R848. In agreement with our nursery study, R848 conjugated to influenza virus induced a higher antibody response in neonates compared to the non-adjuvanted vaccine. Further, the increase in the response relative to that induced by the non-adjuvanted vaccine was maintained at 6 months suggesting the increased antibody secreting cells that resulted from inclusion of conjugated R848 production were capable of surviving long term. There was no significant difference in quality of antibody (i.e. neutralization or affinity), suggesting the beneficial effect of conjugated R848 during vaccination of neonates with inactivated influenza virus is likely manifest during the early generation of antibody secreting cells.

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Section: Discussionmentioning

confidence: 99%

Adjuvanting an inactivated influenza vaccine with conjugated R848 improves the level of antibody present at 6 months in a nonhuman primate neonate model

Holbrook

D’Agostino

Aycock

et al. 2017

Vaccine

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“…112,123 In addition to chemokine receptor expression, cTfh cells can also be divided into "activated" and "resting" subsets based on PD-1 expression, with the PD-1 hi "activated" population most efficiently promoting B cell differentiation into antibodysecreting cells with IgG production. 112,123 In addition to chemokine receptor expression, cTfh cells can also be divided into "activated" and "resting" subsets based on PD-1 expression, with the PD-1 hi "activated" population most efficiently promoting B cell differentiation into antibodysecreting cells with IgG production.…”

Section: Tfh Cell S In the B Loodmentioning

confidence: 99%

T follicular helper cell heterogeneity: Time, space, and function

Song

Craft

2019

Immunological Reviews

163

136

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Summary T follicular helper (Tfh) cells play a crucial role in orchestrating the humoral arm of adaptive immune responses. Mature Tfh cells localize to follicles in secondary lymphoid organs (SLOs) where they provide help to B cells in germinal centers (GCs) to facilitate immunoglobulin affinity maturation, class‐switch recombination, and generation of long‐lived plasma cells and memory B cells. Beyond the canonical GC Tfh cells, it has been increasingly appreciated that the Tfh phenotype is highly diverse and dynamic. As naive CD4+ T cells progressively differentiate into Tfh cells, they migrate through a variety of microanatomical locations to obtain signals from other cell types, which in turn alters their phenotypic and functional profiles. We herein review the heterogeneity of Tfh cells marked by the dynamic phenotypic changes accompanying their developmental program. Focusing on the various locations where Tfh and Tfh‐like cells are found, we highlight their diverse states of differentiation. Recognition of Tfh cell heterogeneity has important implications for understanding the nature of T helper cell identity specification, especially the plasticity of the Tfh cells and their ontogeny as related to conventional T helper subsets.

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“…Of note, cTfh are not all identical in their transcriptional profile or ability to provide B cell help 124 . Circulating Tfh have been described as being polarized towards Th1, Th2, and Th17 cells, while cTfh that express ICOS and other markers of activation have been shown to contain vaccine-specific responses 36,84,120,124 . Moving forward, it will be critical to define the ways in which cTfh can reflect the ongoing lymph node biology of HIV infection and immune dysfunction.…”

Section: Cd4+ T Cells In Human and Non-human Primate Chronic Viral Inmentioning

confidence: 99%

CD4+ T Cell Differentiation in Chronic Viral Infections: The Tfh Perspective

Vella

Herati

Wherry

2017

Trends in Molecular Medicine

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CD4+ T cells play a critical role in the response to chronic viral infections during the acute phase and in the partial containment of infections once chronic infection is established. As infection persists, the virus-specific CD4+ T cell response begins to shift in phenotype. The predominant change described in both mouse and human studies of chronic viral infection is a decrease in detectable Th1 responses. Some Th1 loss is due to decreased proliferative potential and decreased cytokine production in the setting of chronic antigen exposure. However, recent data suggest that Th1 dysfunction is accompanied by a shift in the differentiation pathway of virus-specific CD4+ T cells, with enrichment for cells with a T follicular helper cell (Tfh) phenotype. A Tfh-like program during chronic infection has now been identified in virus-specific CD8+ T cells as well. In this review, we discuss what is known about CD4+ T cell differentiation in chronic viral infections, with a focus on the emergence of the Tfh program and the implications of this shift with respect to Tfh function and the host-pathogen interaction.

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ICOS+PD-1+CXCR3+ T follicular helper cells contribute to the generation of high-avidity antibodies following influenza vaccination

Cited by 151 publications

References 25 publications

Adjuvanting an inactivated influenza vaccine with conjugated R848 improves the level of antibody present at 6 months in a nonhuman primate neonate model

Adjuvanting an inactivated influenza vaccine with conjugated R848 improves the level of antibody present at 6 months in a nonhuman primate neonate model

T follicular helper cell heterogeneity: Time, space, and function

CD4+ T Cell Differentiation in Chronic Viral Infections: The Tfh Perspective

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