HSV2の発症・再発メカニズム！すごいぞ！CD8αα + T-cells

今回新たに発見された、

　　免疫細胞　CD8αα + T-cells

により、性器ヘルペス（HSV2）の発症・再発メカニズムが明らかになってきました！

2013年5月8日に公表された、「A vaccine for herpes? Researchers discover immune cells that suppress HSV-2 infection（ヘルペスワクチン？HSV2感染を抑制する免疫細胞を発見！）」という記事を見てみると…、

• "What we found was that (these T-cells) are turned on and making all sorts of antiviral substances,"
  
  これらのT細胞（免疫細胞＝CD8αα + T-cells）がオンになると抗ウィルス物質が生成される
• "When the virus reactivates, they are the first cells in to contain the virus, and we showed they contain it very well. They can contain it before the virus escapes above the skin."
  
  ウイルスが再活性すると、まず最初にこれらの免疫細胞がウイルスを取り込み、皮膚の表面にウイルスが出てくるのを阻止している

という仕組みになっているようで、その免疫細胞の多くが「 真皮・上皮接合部 Dermal-epidermal junction (DEJ)」に存在していることが分かったようです。

これまでは、HSV2の再発は脊柱管（Spinal Carnal Area）の神経節で調整されていると考えられていたようですが、今回採用した、レーザー光を用いて組織切片から特定の細胞を切り出す「レーザーマイクロダイセクション：Laser Capture Microdissection」により、実はCD8αα + T-cellsが真皮・上皮接合部に多く存在していることが分かったようなんです！


読者の中には、

　　「で、肝心の再発の仕組みはどうなるのよ？」 (-_-メ)

と言われる方もいらっしゃるでしょうが…、それについては…、どうやら以下の部分が説明しているようです…。

Not only did the research team make this significant discovery about the T-cells’ location, they also found that the CD8αα+ T-cells are programmed to remain in the skin surrounding the genitals at all times – making them resident memory T-cells.  The cells’ long-term persistence may explain why patients have asymptomatic recurrences of genital herpes, because the cells are constantly doing “immune surveillance” – always working to find and destroy HSV-2. 

“The real implication here is that the way herpes seems to act is that the virus is actually reactivating very frequently,” Corey said.  “The human immune response is containing it most of the time.”

Researchers had originally estimated that herpes reactivated once a month, but the discovery of these ever-present T-cells led Corey and his team to believe the virus actually reactivates once a week or every few days.  So when herpes lesions occur, it is because there were not enough CD8αα+ T-cells to suppress the outbreak, Corey said. 

この説明の中で面白かったのは、

1. CD8αα+ T-cellsは、性器の皮膚下で常時待機しているようで、これはつまり、HSV2ウイルスに対する免疫上の監視を行っているのではないだろうか？
2. そうすると…、HSV2ウイルスは、これまで考えられていた（これまでは、平均約月1回再発すると考えられていた）よりも頻繁に活性化していて、ひょっとしたら、週ごとに、または数日ごとに活性化しているのではないか？
3. そして、度重なる活性化などの理由で、CD8αα+ T-cellsの数が十分でなかった時に、症状が再発する。

と仮説を立てているところでした！

それにしても、分析の方法が進めば、色々と新しく分かることも増えてくるものなんですね…！



A vaccine for herpes? Researchers discover immune cells that suppress HSV-2 infection

By Loren Grush

Published May 08, 2013

FoxNews.com

Genital herpes is one of the most common types of sexually transmitted infections (STI) in the United States – as well as one of the most frustrating.  Characterized by periodic blisters on the genitals, rectum or mouth, there is currently no cure for the disease, and it can only be managed by antiviral medications which help shorten outbreak periods.

However, a new study may provide hope for those suffering from this STI. Researchers have identified a subtype of immune cells that suppress outbreaks of genital herpes caused by the herpes simplex virus type 2 (HSV-2).

The discovery could lead to a vaccine capable of preventing herpes lesions on people who have already contracted the STI – or in other words, a vaccine that could “clinically cure” an individual of herpes symptoms.

The newly identified T-cells, called CD8αα+ T-cells, reveal a great deal more information about genital herpes than was initially known.

“What we found was that (these T-cells) are turned on and making all sorts of antiviral substances,” lead author Dr. Larry Corey, an internationally renowned virologist and president and director of the Fred Hutchinson Cancer Research Center in Seattle, Wash., told FoxNews.com.  “When the virus reactivates, they are the first cells in to contain the virus, and we showed they contain it very well. They can contain it before the virus escapes above the skin.”

Before this study, researchers believed that herpes reactivation was controlled at the ganglion level of the spinal canal area. But by using a technique called laser capture, Corey and his colleagues were able to biopsy and analyze the RNA in pieces of human tissue from the dermal-epidermal junction (DEJ), where the dermis – the outer layer of skin – connects to the epidermis – the layer of tissue just below the skin’s surface.  The team discovered that these CD8αα+ T-cells are located in the DEJ and are responsible for controlling HSV-2 – implying that herpes reactivation is controlled in the skin, not the spine.

Not only did the research team make this significant discovery about the T-cells’ location, they also found that the CD8αα+ T-cells are programmed to remain in the skin surrounding the genitals at all times – making them resident memory T-cells.  The cells’ long-term persistence may explain why patients have asymptomatic recurrences of genital herpes, because the cells are constantly doing “immune surveillance” – always working to find and destroy HSV-2.
“The real implication here is that the way herpes seems to act is that the virus is actually reactivating very frequently,” Corey said.  “The human immune response is containing it most of the time.”

Researchers had originally estimated that herpes reactivated once a month, but the discovery of these ever-present T-cells led Corey and his team to believe the virus actually reactivates once a week or every few days.  So when herpes lesions occur, it is because there were not enough CD8αα+ T-cells to suppress the outbreak, Corey said.

CD8αα+ T-cells were previously known to exist in the gut mucosa, but most of the research on CD8+ T-cells focused on studying them in blood circulation.  Corey and his team were the first to find the phenotype of CD8αα+ T-cells to persist in the skin.  He said that a potential herpes vaccine would focus on increasing these cells in the immune system.

“It gives us a marker by which one can test vaccines,” Corey said.  “A vaccine that will increase the number or function of these cells would be one you would want to develop.  I don’t think there would be any side effects.”

The vaccine could potentially stop individuals from experiencing outbreaks – the times when a person is most contagious.  Generally, a person can only contract HSV-2 infections during sexual intercourse with an infected individual; however, transmission can still occur when the infected individual does not have a visible sore.

According to the Centers for Disease Control and Prevention, 776,000 people in the United States are infected with herpes each year, and one out of six people between the ages of 14 and 49 have genital HSV-2 infection. While this vaccine would not cure those of HSV-2, it could ultimately help stop the spread of this very prevalent STI.

“We think it’s possible to contain,” Corey said.  “It’s a ‘clinical cure.’”

http://hnews.us/2013/05/08/significant-breakthrough-in-hsv-understanding/