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Scientists identify Tox2 as an important regulator of TFH immune cells

Figure 1. Tonsil GCTFH cells express abundant Tox2 and are positively correlated with BCL6 and PDCD1. -ICOS- as a naive CD4. (B) mRNA expression of TOX, TOX2, and TFH-related genes as assessed by NanoString in human tonsil CD4 + T cell subsets. * NS

Vaccines have been the mainstay of modern medicine since the late 18th century, but there is evidence that society has been using vaccines for over 1000 years. During this time, all vaccines have worked by activating various immune cells against infection.New research Science Advances Professor Hideki Ueno, led by ASHBi, reports how the transcription factor Tox2 regulates the activation of one of these cells, the TFH cell.

One of the most effective ways for the body to fight infections is antibody.. Antibodies are not easy to make in the laboratory, but vaccines stimulate the body’s production of antibodies against certain infectious diseases, such as SARS-CoV-2, the virus that causes the COVID-19 pandemic.

Number of Immune cells Involved in antibody production including TFH cell, Or T follicular helper cells.

“TFH cells are essential for the production of high-affinity antibodies and long-lived antibody-producing cells,” Ueno said. In other words, the TFH cells themselves do not make antibodies, but their function has a significant effect on the immune cells that make the antibodies. In fact, many antibody disorders are associated with their dysfunction.

Reaffirming that these cells are important in combating infection or adaptive immunity is evidence that they are present in the blood even decades after vaccination and have immunological memory. It describes the ability to react quickly when a pathogen is encountered a second time. Ueno argues that understanding the molecules that enable this persistence will help vaccine research.

“NS Molecular mechanism What is associated with a sustained TFH cellular response is unknown. It turns out that Tox2 expression is important. “

Tox2 has been shown to contribute to the depletion of immune cells. The depletion of immune cells is a discovery that led to the 2018 Nobel Prize for Professor Saku Honjoda of Kyoto University. Cell depletion is a natural effect that not only prevents the development of autoimmune diseases, but also allows cancer to persist.

However, a new study found that Tox2 has very different effects on TFH cells.

“Our study shows that Tox2 is important for long-term survival and function maintenance of TFH cells, suggesting a different role than other T cells,” Ueno said.

To test this hypothesis, Ueno et al. Conducted two experiments. One is the overexpression of Tox2 in human TFH cells. On the other hand, they prevented its expression in mice.

Normally, human TFH cells are transformed into other types of immune cells by immune stimulation. However, human TFH cells overexpressing Tox2 were stable.

“TFH cells are not ultimately differentiated and are naturally transformed by TCR stimulation,” Ueno said. “Overexpression of Tox2 was found to isolate cells from this spontaneous transformation. This finding indicates that Tox2 is important for the persistence of TFH cells.”

In contrast, Tox2-deficient mice had low levels of TFH cells in their blood and had an inadequate antibody response to infection.

Experiments suggest that targeting Tox2 can be used therapeutically to regulate TFH cells.

“Our findings demonstrate the importance of Tox2 for the maintenance of TFH cells and the establishment of TFH cell memory, which is an important insight in the development of vaccines that elicit strong and durable antibody responses. “We will provide,” said Mr. Ueno.


Studies show that more memory B cells are present in those who have been completely vaccinated with a previous SARS-CoV-2 infection.


For more information:
Shu Horiuchi et al, Tox2 are required for maintenance of GC TFH cells and generation of memory TFH cells. Science Advances (2021). DOI: 10.1126 / sciadv.abj1249

Provided by
Kyoto University

Quote: Scientists have identified Tox2 as a major regulator of TFH immune cells (October 15, 2021).

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Scientists identify Tox2 as an important regulator of TFH immune cells

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