With a Little Help from T Follicular Helper Friends: Humoral Immunity to Influenza Vaccination

Koutsakos, Marios; Nguyen, Thi H. O.; Kedzierska, Katherine

doi:10.4049/jimmunol.1800986

Cited by 62 publications

(56 citation statements)

References 45 publications

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“…Follicular helper T cells (Tfh), with high expression of CXCR5, PD‐1 and ICOS, are critical in germinal centre (GC) reaction of B cells and determine the quality of humoral responses . Circulating Tfh (cTfh) cells in blood are also found, which are probably linked developmentally and functionally to GC Tfh . Other T cell subtypes that provide B cell help are also reported.…”

Section: Discussionmentioning

confidence: 99%

“…33 Circulating Tfh (cTfh) cells in blood are also found, which are probably linked developmentally and functionally to GC Tfh. 45 Other T cell subtypes that provide B cell help are also reported. PD-1 hi CXCR5 − CD4 + T cells, termed peripheral helper T cells (Tph), are expanded in rheumatoid arthritis synovium, which promote plasma cell differentiation and antibody production.…”

Section: Discussionmentioning

confidence: 99%

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PD‐1‐expressing MAIT cells from patients with tuberculosis exhibit elevated production of CXCL13

Jiang

Cao

et al. 2020

Scand J Immunol

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To understand functional role of PD‐1‐expressing MAIT cells during tuberculosis infection in humans, sorted PD‐1+ and PD‐1− MAIT cells from pleural effusions of patients with pleural tuberculosis were subjected to transcriptome sequencing. PD‐1‐expressing MAIT cells were analysed by flow cytometry and their phenotypic and functional features were investigated. Transcriptome sequencing identified 144 genes that were differentially expressed between PD‐1+ and PD‐1− MAIT cells from tuberculous pleural effusions and CXCL13 was the gene with highest fold difference. The level of PD‐1‐expressing MAIT cells was associated with extent of TB infection in humans. PD‐1‐expressing MAIT cells had increased production of CXCL13 and IL‐21 as determined by flow cytometry. PD‐1highCXCR5− MAIT cells were significantly expanded in pleural effusions from patients with pleural tuberculosis as compared with those from peripheral blood of both patients with tuberculosis and healthy controls. Although PD‐1highCXCR5− MAIT cells from tuberculous pleural effusions had reduced IFN‐γ level and increased expression of Tim‐3 and GITR, they showed activated phenotype and had higher glucose uptake and lipid content. It is concluded that PD‐1‐expressing MAIT cells had reduced IFN‐γ level but increased production of both CXCL13 and IL‐21.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

PD‐1‐expressing MAIT cells from patients with tuberculosis exhibit elevated production of CXCL13

Jiang

Cao

et al. 2020

Scand J Immunol

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“…CD4 T cell help is essential for production of high affinity antibodies in response to vaccination (reviewed in refs [1][2][3] ). The nature and complexity of the immunogen within vaccines will therefore affect the specificity and abundance of CD4 T cell responses and thus potentially the magnitude and quality of the elicited antibody.…”

Section: Introductionmentioning

confidence: 99%

Heterologous viral protein interactions within licensed seasonal influenza virus vaccines

et al. 2020

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Currently, licensed influenza virus vaccines are designed and tested only for their ability to elicit hemagglutinin (HA)-reactive, neutralizing antibodies. Despite this, the purification process in vaccine manufacturing often does not completely remove other virion components. In the studies reported here, we have examined the viral protein composition of a panel of licensed vaccines from different manufacturers and licensed in different years. Using western blotting, we found that, beyond HA proteins, there are detectable quantities of neuraminidase (NA), nucleoprotein (NP), and matrix proteins (M1) from both influenza A and influenza B viruses in the vaccines but that the composition differed by source and method of vaccine preparation. We also found that disparities in viral protein composition were associated with distinct patterns of elicited antibody specificities. Strikingly, our studies also revealed that many viral proteins contained in the vaccine form heterologous complexes. When H1 proteins were isolated by immunoprecipitation, NA (N1), M1 (M1-A), H3, and HA-B proteins were co-isolated with the H1. Further biochemical studies suggest that these interactions persist for at least 4 h at 37°C and that the membrane/intracytoplasmic domains in the intact HA proteins are important for the intermolecular interactions detected. These studies indicate that, if such interactions persist after vaccines reach the draining lymph node, both dendritic cells and HA-specific B cells may take up multiple viral proteins simultaneously. Whether these interactions are beneficial or harmful to the developing immune response will depend on the functional potential of the elicited virus-specific CD4 T cells.

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“…TFH drive GCB formation which leads to B cell isotype class switching, generation of high affinity somatically mutated B cells, and generation of long-lived plasma cells and memory B cells (Crotty, 2019). TFH are required for, and are a reliable indicator of, protective Ab after influenza vaccination (Koutsakos et al, 2019b). ThCTL reduce viral titers and are associated with better disease control in many viral infections (Juno et al, 2017;Muraro et al, 2017;Phetsouphanh et al, 2017) and tumor models (Melssen and Slingluff, 2017), especially those where class I is downregulated by viruses and tumor microenvironments where CD8 cytotoxic cells are ineffective.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic CD4 Development Requires CD4 Effectors to Concurrently Recognize Local Antigen and Encounter Infection-Induced IL-15

Devarajan

Vong

Castonguay

et al. 2020

Preprint

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SummaryT follicular helper (TFH) and Cytotoxic CD4 (ThCTL) are tissue-restricted CD4 effector subsets, functionally specialized to mediate optimal Ab production and cytotoxicity of infected cells. Influenza infection generates robust CD4 responses, including lung ThCTL and SLO TFH, that protect against reinfection by variant strains. Antigen (Ag) presentation after infection, lasts through the effector phase of the response. Here, we show that this effector phase Ag presentation, well after priming, is required to drive CD4 effectors to ThCTL and TFH. Using in vivo influenza models, we varied Ag presentation to effectors acutely, just at the effector phase. Ag presentation was required in the tissue of effector residence. We suggest these requirements contain unnecessary or potentially pathogenic CD4 responses, only allowing them if infection is uncleared. The results imply that providing effector phase Ag, would lead to stronger humoral and CD4 tissue immunity and thus can be applied to improve vaccine design.

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With a Little Help from T Follicular Helper Friends: Humoral Immunity to Influenza Vaccination

Cited by 62 publications

References 45 publications

PD‐1‐expressing MAIT cells from patients with tuberculosis exhibit elevated production of CXCL13

PD‐1‐expressing MAIT cells from patients with tuberculosis exhibit elevated production of CXCL13

Heterologous viral protein interactions within licensed seasonal influenza virus vaccines

Cytotoxic CD4 Development Requires CD4 Effectors to Concurrently Recognize Local Antigen and Encounter Infection-Induced IL-15

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