What needs to happen in the immune system to make the body more resistant to COVID-19 infection

T cells are white blood cells that mature in the thymus, an organ located below the breastbone. They develop from birth to 25 years old, and circulate in the blood and lymph. When the body is first attacked by a pathogen, an innate immune response first appears. Later, The T cells of the adaptive immune system are activated to remove the remains of the pathogen. Some of these cells later turn into “memory” T cells and persist in the body.

Nail new research conducted in the United States helped provide more clarity on what happens to immune system responses to coronavirus infection that causes COVID-19 disease. It was discovered during the study of monkeys that T cells are not essential for the recovery of primates after acute COVID-19 infections.

Depletion of T cells does not induce serious disease, and T cells do not explain the natural resistance of rhesus macaque monkeys to severe COVID-19. Additionally, macaques with reduced T cell levels continue to develop powerful memory responses to a second infection.

The research results were published in mBio, an open access journal of the American Society for Microbiology, and have implications for the development of second-generation vaccines and therapies.

Since the start of the pandemic, hundreds of laboratories around the world have focused on investigating the coronavirus infection. Some concentrated prevention measures. Others in the development of the infection itself and its impact on the body. There are also groups focused on vaccines and treatments.

“We started this study early in the pandemic, trying to figure out how to create a good model to study the disease in humans using animals. The monkeys have been shown to be more resistant to the disease than we expected, so we wanted to find out why and try to get a feel for the disease in humans. “ said the study’s lead author, Kim Hasenkrug, senior researcher at the Persistent Viral Diseases Laboratory, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.

“We now know that the antibody response is the most critical for protection by vaccination, not the T cell response.” In the new study, the researchers used classic reagents known to lower the levels of CD4 + and CD8 + T cells in the rhesus monkeys.

While CD8 + T cells directly attack and kill infected cells, CD4 + T cells are helper T cells that trigger the immune response by recognizing pathogens and secreting cytokines, small proteins, that signal to d ‘other immune cells to act, including CD8 + T cells and antibody-producing B cells.

A week after killing CD4 + T cells, CD8 + T cells, or both at the same time, the researchers infected the animals with the coronavirus. After reducing the levels of T cells, they infected them, and then we continued the depletions during the first week of infection, ”Hasenkrug said. They then did blood tests to see how they reacted in terms of T and B cells.

For six weeks, researchers studied nasal swabs and bronchoalveolar washes to measure virus in the nose, mouth, and lungs, and rectal swabs to see if the gut was excreting the virus. After six weeks, The researchers again challenged the monkeys with the coronavirus and repeated the virus and the blood sample, allowing the researchers to assess immune memory responses.

“If there’s a memory response, you get a much faster immune response and virus control. This is how vaccines work. Once the body sees a viral pathogen, the next time it sees it, it can get a much faster and stronger immune response, ” says Dr Hasenkrug.

The researchers found that the monkeys were able to create a good memory response against the virus, regardless of the reduction in T cells. “We found that we got very good memory responses whether or not we were reducing T cells. Basically we find neutralizing antibodies to viruses very strong, and these are the most important antibodies for controlling infection. This was unexpected for most immunologists, virologists and vaccinators, ”Hasenkrug said.

“The other thing that happens during a memory response is that the antibodies mature, becoming stronger and more potent to bind to the viral pathogen. We have seen indications of this through what is called “class change,” Hasenkrug said.

The “class shift” was also unexpected in these T cell depleted monkeys. “We don’t have a specific explanation as to why this happened, but we believe it involves some sort of compensatory response, which can be seen in our study. For example, when we kill CD8 + T cells, we see stronger CD4 + T cell or B cell responses in some animals. When animals lack something, they try to make up for it by producing more of something else ”.

Hasenkrug isn’t sure why T cells haven’t turned out to be more important, but it’s probably a good thing they aren’t needed, as people who fail to develop enough T cell responses still have a problem. chance to bounce back.

“This implies that the innate immune response is essential for the initial control of the virus, rather than the adaptive immune responses that we have studied,” explains Hasenkrug.

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