Can follicular helper T cells be targeted to improve vaccine efficacy?

Linterman, Michelle A.; Hill, Danika L.

doi:10.12688/f1000research.7388.1

Cited by 89 publications

(79 citation statements)

References 122 publications

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“…The size and quality of the GC response are directly affected by Tfh cells, which provide growth and differentiation signals to GC B cells and mediate positive selection of high-affinity B cell clones in the GCs (35,36). In our study, significantly more GC B cells were detected in the mice immunized with rLBNSE-IL-7 than in the mice immunized with rLBNSE.…”

Section: Discussionmentioning

confidence: 47%

Overexpression of Interleukin-7 Extends the Humoral Immune Response Induced by Rabies Vaccination

Zhou

Luo

et al. 2017

J Virol

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Rabies continues to present a public health threat in most countries of the world. The most efficient way to prevent and control rabies is to implement vaccination programs for domestic animals. However, traditional inactivated vaccines used in animals are costly and have relatively low efficiency, which impedes their extensive use in developing countries. There is, therefore, an urgent need to develop single-dose and long-lasting rabies vaccines. However, little information is available regarding the mechanisms underlying immunological memory, which can broaden humoral responses following rabies vaccination. In this study, a recombinant rabies virus (RABV) that expressed murine interleukin-7 (IL-7), referred to here as rLBNSE-IL-7, was constructed, and its effectiveness was evaluated in a mouse model. rLBNSE-IL-7 induced higher rates of T follicular helper (Tfh) cells and germinal center (GC) B cells from draining lymph nodes (LNs) than the parent virus rLBNSE. Interestingly, rLBNSE-IL-7 improved the percentages of long-lived memory B cells (Bmem) in the draining LNs and plasma cells (PCs) in the bone marrow (BM) for up to 360 days postimmunization (dpi). As a result of the presence of the long-lived PCs, it also generated prolonged virus-neutralizing antibodies (VNAs), resulting in better protection against a lethal challenge than that seen with rLBNSE. Moreover, consistent with the increased numbers of Bmem and PCs after a boost with rLBNSE, rLBNSE-IL-7-immunized mice promptly produced a more potent secondary anti-RABV neutralizing antibody response than rLBNSE-immunized mice. Overall, our data suggest that overexpressing IL-7 improved the induction of long-lasting primary and secondary antibody responses post-RABV immunization.IMPORTANCE Extending humoral immune responses using adjuvants is an important method to develop long-lasting and efficient vaccines against rabies. However, little information is currently available regarding prolonged immunological memory post-RABV vaccination. In this study, a novel rabies vaccine that expressed murine IL-7 was developed. This vaccine enhanced the numbers of Tfh cells and the GC responses, resulting in upregulated quantities of Bmem and PCs. Moreover, we found that the long-lived PCs that were elicited by the IL-7-expressing recombinant virus (rLBNSE-IL-7) were able to sustain VNA levels much longer than those elicited by the parent rLBNSE virus. Upon reexposure to the pathogen, the longevous Bmem, which maintained higher numbers for up to 360 dpi with rLBNSE-IL-7 compared to rLBNSE, could differentiate into antibody-secreting cells, resulting in rapid and potent secondary production of VNAs. These results suggest that the expression of IL-7 is beneficial for induction of potent and long-lasting humoral immune responses.KEYWORDS IL-7, humoral immunity, rabies virus

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Section: Discussionmentioning

confidence: 47%

Overexpression of Interleukin-7 Extends the Humoral Immune Response Induced by Rabies Vaccination

Zhou

Luo

et al. 2017

J Virol

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“…Both peripheral circulating and germinal center (GC) Tfh cells support B‐cell activation, expansion and differentiation into plasma cells and memory B cells in GC, thereby promoting B‐cell immunity . Human circulating Tfh cells are divided into three major functional subtypes (Tfh1, Tfh2, and Tfh17), with skewing to Tfh2 and Tfh17 subtypes observed in autoimmune disease and several tumors …”

Section: Introductionmentioning

confidence: 99%

Functionally impaired follicular helper T cells induce regulatory B cells and CD14⁺ human leukocyte antigen‐DR⁻ cell differentiation in non‐small cell lung cancer

Qiu

Zhou

et al. 2018

Cancer Science

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Non‐small cell lung cancer (NSCLC) represents one of the most common and aggressive cancers worldwide, as it typically displays irreversible progression and poor prognosis. Interaction between programmed death 1 (PD‐1) and its ligand, PD‐L1, plays important roles in tumor immunology. Follicular helper T (Tfh) cells have characteristically high PD‐1 expression; thus, in the present study, we investigated the role of circulating Tfh cells and their correlation with disease‐free survival after tumor resection in NSCLC. We found significantly higher number of Tfh cells but lower serum interleukin (IL)‐21 levels in NSCLC patients, especially in those with advanced stage (III and IV), indicating that the function of Tfh cells to produce IL‐21 was impaired. Further analysis showed that the increase in Tfh cells was attributable to an expansion of the PD‐1+‐Tfh2 and PD‐1+‐Tfh17 subtypes. Functional analysis showed that Tfh cells from NSCLC patients induced the differentiation of regulatory B cells and CD14+ human leukocyte antigen (HLA)‐DR − cells. Interestingly, the number of Tfh1 subtypes in NSCLC patients was negatively correlated with disease‐free survival after tumor resection. In short, the high number and abnormal function of Tfh cells could cause further immunosuppression and lead to tumor development in NSCLC. Rescuing Tfh functions therefore represents a potential therapeutic strategy in NSCLC.

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“…As an important component of the immune response to viral infection, T FH cells have a contributory role in autoimmunity (2). Recent analysis of human blood identified 3 major functional subsets (T FH 1, T FH 2, and T FH 17) (3), with specific T FH subsets correlated with broad neutralizing anti-viral Ab or auto-Ab (4).…”

Section: T Follicular Helper Cells (T Fh Cells) Are a Functionally DImentioning

confidence: 99%

CXCL13-producing TFH cells link immune suppression and adaptive memory in human breast cancer

Gu-Trantien¹,

Migliori²,

Buisseret³

et al. 2017

JCI Insight

290

283

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Can follicular helper T cells be targeted to improve vaccine efficacy?

Cited by 89 publications

References 122 publications

Overexpression of Interleukin-7 Extends the Humoral Immune Response Induced by Rabies Vaccination

Overexpression of Interleukin-7 Extends the Humoral Immune Response Induced by Rabies Vaccination

Functionally impaired follicular helper T cells induce regulatory B cells and CD14⁺ human leukocyte antigen‐DR⁻ cell differentiation in non‐small cell lung cancer

CXCL13-producing TFH cells link immune suppression and adaptive memory in human breast cancer

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Can follicular helper T cells be targeted to improve vaccine efficacy?

Cited by 89 publications

References 122 publications

Overexpression of Interleukin-7 Extends the Humoral Immune Response Induced by Rabies Vaccination

Overexpression of Interleukin-7 Extends the Humoral Immune Response Induced by Rabies Vaccination

Functionally impaired follicular helper T cells induce regulatory B cells and CD14+ human leukocyte antigen‐DR− cell differentiation in non‐small cell lung cancer

CXCL13-producing TFH cells link immune suppression and adaptive memory in human breast cancer

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Functionally impaired follicular helper T cells induce regulatory B cells and CD14⁺ human leukocyte antigen‐DR⁻ cell differentiation in non‐small cell lung cancer