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Studies show that T cells are not important for primate recovery from acute COVID-19 infection

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A new study done in monkeys reveals that T cells Not important for recovery of primates from acute COVID-19 infection. T cell depletion does not induce serious disease, and T cells do not explain the natural resistance of rhesus monkeys to severe COVID-19. In addition, macaques, which are strongly T-cell depleted, show a strong memory response to the second infection.

Survey results published in mBioThe American Society for Microbiology’s open access journal, is influencing the development of second-generation vaccines and therapies.

“We started this study early in the pandemic and sought to find a way to use animals to create good models for studying human disease. Monkeys are more resistant to disease than expected. Now that we know why, we try to understand why it was and gain some insight into human illnesses, “says the National Institute for Allergic Infectious Diseases, Rocky Mountain Institute, Institute for Persistent Viral Diseases. Said Dr. Kim Hasenkrug, Principal Investigator and Principal Investigator. National Institutes of Health in Hamilton, Montana. “The antibody response turned out to be the most important response to protection by vaccination, not the T cell response.”

In the new study, researchers used classics reagent It is known to deplete CD4 + and CD8 + T cells in rhesus monkeys. While CD8 + T cells directly attack and kill infected cells, CD4 + T cells are cytokines that recognize pathogens and signal to act on CD8 + T cells and other immune cells, including antibody production. Helper T cells that provoke an immune response by secreting small proteins. B cells.

One week after simultaneous depletion of CD4 + T cells, CD8 + T cells, or both macaques, researchers infected animals with SARS-CoV-2. “We depleted, infected, and continued to deplete during the first week of infection, confirming that the animals were fully depleted. Next, we examined the blood and looked at the T and B cells perspectives. I looked at how it was reacting from, “Hazen Kruk said. For six weeks, the researchers examined the nasal swab and bronchoalveolar lavage fluid to measure nasal, mouth, and lung viruses, and examined the rectal swab to see if the intestines were shedding the virus. Six weeks later, the researchers re-challenge the monkeys with SARS-CoV-2 and repeat the collection of virus and blood samples. This allowed researchers to assess the immunological memory response. “A memory response makes the immune response and virus control much faster. This is the mechanism of vaccination. When the body detects a viral pathogen, it is much faster and faster the next time it detects the virus. A strong immune response. “

Researchers have found that monkeys can initiate a good memory response to the virus regardless of T cell depletion. “We found that we had a really good memory response, whether or not we depleted T cells. Basically, we found a very powerful virus. Neutralizing antibody, And they are the most important antibodies in controlling infection. This was unexpected for most immunologists, virologists and vaccinologists, “says Hazenkrug.

“Another thing that happens during the memory response is that the antibody matures and becomes stronger and stronger in binding to viral pathogens, which has been demonstrated through so-called” class switches “,” Hazen said. Krug said.

The “class switch” was also unexpected in these T cell-depleted monkeys. “There is no clear explanation as to why it happened, but I think it involves some kind of compensatory response that we can see in our study. For example, depleting CD8 + T cells makes it stronger. CD4 + T cells have been seen or B cells react in some animals. When an animal is losing something, they try to make up for it by making something more. . “

Hazen Kruk doesn’t know why T cells didn’t turn out to be more important, but people who can’t mount a sufficient T cell response still have a chance to recover, so T cells aren’t needed. Probably a good thing.

“This means that the innate immune response, not the adaptive immune response we studied, is important for the initial control of the virus,” says Hazenkrug.

sauce:

Journal reference:

Hazen Kruk, KJ, et al. (2021) Recovery from acute SARS-CoV-2 infection and development of pre-existing immune response in T cell-depleted rhesus monkeys. mBio.. doi.org/10.1128/mBio.01503-21..

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