Trevor James
The efficacy of influenza vaccines depends on the vaccine recipient and the similarity of the vaccine to the endemic virus. Regulatory T cells (Tregs) and cytokines are known to restrict immune responses against viral infections. The degree of immunity within an influenza virus subtype depends on previous exposure to natural infection, the individual’s immune status, and the immunity developed through annual influenza vaccinations. Studies have shown that repeat influenza vaccination reduces antibody induction and impairs the affinity maturation of influenza-specific antibodies. However, it is unclear whether this association can be observed on an antigen-specific level. Research has also shown that influenza vaccination stimulates maturation of the human T follicular helper cell response. T follicular helper cells have been observed to persist in the lymph nodes 3-6 months after the first vaccination and reappeared in year 2 upon revaccination.
| Characteristics | Values |
|---|---|
| T-cell response to influenza vaccine | T-cell response to the influenza vaccine varies depending on the individual's immune status, vaccination history, and the similarity of the vaccine to the endemic virus. |
| T-cell type involvement | Regulatory T cells (Tregs), CD4+ T cells, CD8+ T cells, and cytotoxic T cells (CTLs) are involved in the immune response to the influenza vaccine. |
| T-cell response duration | T-cell responses to the influenza vaccine can persist for up to 6 months and reappear upon revaccination. |
| T-cell response variation | The T-cell response to the influenza vaccine can vary between individuals, with some exhibiting stronger responses than others. |
| T-cell response in special populations | Organ transplant recipients on immunosuppressive therapies may have altered T-cell responses to the influenza vaccine. |
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What You'll Learn
T follicular helper cell response
T follicular helper cells (TFH) are a subset of CD4+ T cells that play a crucial role in the immune response to influenza vaccination. TFH cells interact with B cells in the germinal centres (GCs) of lymph nodes, leading to the production of antibodies that provide protection against influenza viruses.
Following influenza vaccination, TFH cells undergo maturation and clonal expansion. A study by Schattgen et al. examined the dynamics and clonal evolution of CD4+ TFH cells in human volunteers who received two influenza vaccines one year apart. They observed a transient increase in circulating TFH cell frequencies in the blood during the first two weeks after the first vaccination. The TFH cells then clonally expanded and slowly matured into IL21+CXCL13+ GC TFH cells. Upon revaccination one year later, the shift towards a GC TFH cell phenotype occurred with faster kinetics.
The presence of influenza-specific TFH cell clonotypes has been detected in lymph nodes 3-6 months after the first vaccination, persisting for up to 4 months. These TFH cells displayed memory-based responses, targeting conserved epitopes present in split-inactivated vaccines rather than new responses to desired epitopes. This persistence of TFH cells suggests that they contribute to long-term immunity against influenza.
The formation of circulating T follicular helper (cTfh) cells has been associated with high-titre antibody responses to influenza vaccination. However, impaired TFH cell responses have been linked to inflammation in humans, particularly in older individuals. Dysfunctional peripheral TFH cells can lead to inadequate vaccine responses, and approaches to target inflammation or expand functional TFH cells may improve vaccine efficacy in aging populations.
In summary, the T follicular helper cell response to influenza vaccination involves the maturation and clonal expansion of TFH cells, leading to antibody production and the establishment of immunological memory. Understanding the dynamics of TFH cells is crucial for optimizing vaccine design and enhancing protective immunity against influenza.
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CD4+ T-cell responses
CD4+ T-cells play a critical role in the immune response to influenza infection and vaccination. CD4+ T-cell responses to influenza vaccines have been the subject of numerous studies, aiming to understand their dynamics and effectiveness in protecting against the influenza virus.
One study by Schattgen et al. investigated the CD4+ TFH (T follicular helper) cell response to influenza vaccines. The study involved human volunteers who received two influenza vaccines one year apart, and the CD4+ TFH cells in their blood and lymph nodes were analysed over two years. The results showed a transient increase in cTFH (circulating TFH) cell frequencies in the blood during the initial two weeks after vaccination. The LN TFH (lymph node TFH) cells, on the other hand, underwent clonal expansion and slow maturation into IL21+CXCL13+ GC TFH cells. The study also observed the emergence of interleukin (IL)-10+ TFH cells by two months post-vaccination.
Another study by L'Huillier et al. focused on solid organ transplant (SOT) recipients, a population at higher risk for influenza-related complications due to immunosuppression. This study compared CD4+ T-cell responses to natural influenza infection and influenza vaccination in SOT patients. It was found that natural influenza infection triggered a significant increase in CD4+ T-cell responses, with polyfunctional cells increasing substantially. However, the vaccine-elicited CD4+ T-cell responses were lower in comparison, indicating that natural infection may provide better protection against reinfection.
The dynamics of CD4+ T-cell memory have also been explored in studies. It has been found that the CD4 T-cell response to influenza can exhibit diverse antigen specificity, depending on the MHC class II molecules expressed. The memory phase of the CD4 T-cell response to influenza infection maintains its diverse antigen specificity, with the specificities detected during the primary response preserved in the memory compartment. This suggests that the initial CD4 memory established after the first encounter with the influenza virus influences the immune response during subsequent encounters.
Furthermore, studies have shown that CD4+ T-cell responses can vary depending on the type of vaccine used. For example, CD4+ TFH cells were found to have an impaired capacity to assist B cells in producing antibodies when they exhibited certain characteristics, such as CXCR3+CXCR5loPD-1lo. This highlights the importance of understanding the complex dynamics of CD4+ T-cell responses to different vaccines and influenza strains.
In conclusion, CD4+ T-cell responses are crucial in the immune response to influenza vaccines. While natural infection may elicit stronger CD4+ T-cell responses, vaccination still plays a vital role in protection against the influenza virus, especially in high-risk populations like SOT recipients. Understanding the dynamics and memory characteristics of CD4+ T-cells can contribute to the development of more effective vaccines and immunisation strategies.
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Cytokine production
Cytokines are small proteins that act as signalling molecules in the immune system, and their production is an important part of the immune response to influenza vaccines.
Research has shown that cytokine production is influenced by influenza vaccination. In one study, the production of IL-10 and IFN-gamma by peripheral blood mononuclear cells (PBMCs) was higher in young individuals compared to the elderly. This study also found that more than 13% of the elderly population did not produce detectable levels of IL-6, IL-10, or IFN-gamma after vaccination. Another study found that antibody titres increased significantly after vaccination in both young and elderly individuals, but the young demonstrated significantly higher titres.
The type of vaccine also influences cytokine production. For example, lower levels of IL-8 were observed after both inactivated influenza vaccine (IIV) and live attenuated influenza vaccines (LAIV). However, post-vaccination antibody levels were higher, and IFN-γ levels were lower in IIV compared to LAIV.
Novel vaccines, such as the E. coli-derived VLP vaccine, have been shown to induce T-cell proliferation and the production of the T helper 1 cytokine IFN-γ. This vaccine also resulted in increased production of IL-10, which is associated with reduced protection against influenza infection.
The presence of CD4+ T-cells specific for the vaccine has been found to be predictive of the long-term maintenance of protective antibody titres. Influenza-specific ICOS+ IL-21+ CD4+ T-cells have also been associated with a rise in functional antibodies, indicating the important role of T-cells in driving humoral immunity following vaccination.
TFH cells have been found to persist in lymph nodes 3-6 months after the first vaccination and reappeared upon revaccination, indicating that the TFH cell response to seasonal influenza vaccination is memory-based. These TFH cells also exhibited rapid redifferentiation and cytokine production in the second year post-vaccination.
In summary, cytokine production is an important aspect of the immune response to influenza vaccines, and various factors such as age, vaccine type, and T-cell responses influence cytokine levels and protection against influenza infection.
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Regulatory T cells
Studies have shown that the frequency of Treg cells, specifically CD4+CD25+ and CD4+Foxp3+ cells, increases significantly two weeks after influenza vaccination. This indicates that Treg cells may be activated post-vaccination, potentially contributing to the regulation of the immune response. The expression of these Treg cells was studied in 24 and 14 subjects, respectively, with the expression frequency of CD4+CD25+ increasing from 0.8 ± 0.6% to 2.5 ± 2.9% post-vaccination. Similarly, the expression frequency of CD4+Foxp3+ increased from 7.1 ± 2.4% to 9.2 ± 2.2%.
Additionally, the plasma levels of certain cytokines, such as transforming growth factor (TGF)-β, were found to increase significantly after vaccination. TGF-β is known to participate in the development and maintenance of Treg subsets and may contribute to the downregulation of the anti-influenza antibody response post-vaccination. On the other hand, interleukin (IL)-10 levels after vaccination were positively correlated with the fold-increases of anti-influenza antibodies, including anti-H1N1 and anti-H3N2.
The role of Treg cells in influenza vaccination is an active area of research, with studies suggesting that altering Treg activity may enhance the efficacy of influenza vaccines. Treg cells may also be influenced by the annual influenza vaccination, as part of the body's immune response to the vaccine.
While the studies provide insights into the role of Treg cells after influenza vaccination, further research is needed to fully understand the dynamics and longevity of Treg cells over time, including their presence 6 months after vaccination.
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T-cell clusters
In the context of influenza vaccines, studies have shown that regulatory T cells (Tregs) play a crucial role in the immune response. Tregs are involved in restricting immune responses against viral infections, and their dynamics after vaccination are important. Increases in CD4+, CD127+, CD4+CD25+, and CD4+Foxp3+ cells have been observed after influenza vaccination, indicating a significant impact on Treg populations.
Additionally, research has explored the impact of influenza vaccines on CD4+ TFH cells, a specific type of T-cell cluster. Studies have found that TFH cells can persist in lymph nodes for up to 6 months after the first vaccination and reappear upon revaccination, demonstrating long-lasting effects. Characterizing the dynamics and clonal evolution of these cells helps understand the immune response to influenza vaccines.
Moreover, T-cell clusters have been studied in specific patient populations, such as solid organ transplant (SOT) recipients. These patients are at increased risk of influenza infection due to immunosuppression. While the influenza vaccine is recommended for SOT recipients, their T-cell responses may be impacted by immunosuppressive therapies. Understanding the dynamics of T-cell clusters in these patients is crucial for optimizing their protection against influenza.
In the context of cancer immunotherapy, T-cell clusters are also being investigated. Tumour-specific T cells can be identified through TCR clustering techniques, aiding in the development of adoptive cell transfer (ACT) therapies. Additionally, CD4+ T-cell clusters have been associated with the efficacy of PD-1 blockade therapy in patients with lung cancer, highlighting the potential for using T-cell clusters to guide tumour treatment.
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Frequently asked questions
T cells are present 6 months after the influenza vaccine. Influenza-specific TFH cell clonotypes persisted in the LN 3–6 months after the first vaccination and reappeared in year 2 upon revaccination.
T cells are a type of white blood cell that plays a crucial role in the immune system's response to foreign invaders such as viruses and bacteria.
T cells help to restrict immune responses against viral infections and play a key role in maintaining lymphoid homeostasis. They also help to shape the CD4+ T cell repertoire after virus elimination.
The influenza vaccine induces the activation of T cells, which can provide protection against the influenza virus. Repeat influenza vaccination may impair antibody maturation, but it also contributes to the development of T cell memory, which is important for long-term protection.
