Finding clues to successful immune responses in T cells of COVID-19 patients

Nadia Roan, Ph.D., a Gladstone Institutes scientist, said on the T cells and their role when news about the new coronavirus switched from recording progress in China to headlines on the global COVID-19 pandemic. I was in the middle of publishing several papers on the spread of HIV and long-term infections.

Besides serving as HIV targets and hideouts, T cells are an important part of the body Immune reaction Against many viruses. They are also the most apparently depleted cell types in severe cases of COVID-19. Roan decided to apply her expertise in T cells to understand people’s response to SARS-CoV-2, the virus that causes COVID-19.

Now, Roan and her team have cataloged T cells in people who recovered from mild cases of COVID-19. Their analysis is Cell report medicineHas clarified what is associated with a successful immune response to SARS-CoV-2 and is impacting vaccine development.

Much of the body’s fight against viruses and other pathogens is done by antibodies that trap specific molecules on the surface of the pathogen and mark them to destroy them. However, antibodies against SARS-CoV-2 infection, It raises concerns that their protective effect may be short-lived.

“Most research on host immunity to SARS-CoV-2 focuses on antibody responses,” says Roan, who is also an Associate Professor of Urology at the University of California, San Francisco. “But other studies also suggest that SARS-CoV-2 can elicit a strong T cell response.”

Therefore, the important question is whether SARS-CoV-2 infection activates T cells, which are long-lived and may confer long-term immunity to the virus. Another question is whether the T cell response can explain why some people recover from an infection after a mild illness, while others succumb to a protracted illness that sometimes leads to death.

To answer these questions, Roan and her team obtained blood samples from nine donors who recovered from SARS-CoV-2 confirmed infections after experiencing only mild symptoms.

“We infer that these patients have a particularly good immune system in eliminating the virus,” says Roan.

Recovered patient cells hold the answer

Roan’s group used a technology called CyTOF. It characterizes T cells according to the proteins they contain or carry to the surface. Different combinations of proteins determine the different roles T cells play in infections and can be used as markers to identify the types of T cells present in human blood. CyTOF can track nearly 40 different protein markers at the same time, allowing researchers to detect many different properties in any cell.

“Knowing the properties of SARS-CoV-2-specific T cells is important to inform us of their functional properties, including their long-lasting ability in convalescent individuals,” Roan says. ..

There are two main types of T cells. CD4 + T cells that play a major role in stimulating the entire immune system’s response to invaders, and CD8 + T cells that kill infected cells. Within these broad categories, CyTOF can distinguish even more subcategories. For example, you can distinguish “short-lived” cells from “effector” T cells, which are “memory” T cells, from “effector” T cells, which are the cells that fight the current infection. infection.

T cells recognize small fragments of pathogen proteins that appear on the surface of infected cells. To reliably investigate patient response to SARS-CoV-2 infection, Roan’s team selected T cells specific for viral proteins. For comparison, we also looked at T cells specific for other viruses, such as influenza and cytomegalovirus.

After subjecting patient samples to CyTOF, Roan’s team discovered an interesting pattern of SARS-CoV-2 specific T cells that could explain how these patients recovered from COVID-19. did.

First, patients with SARS-CoV-2 specific CD4 + T cells belong to a category called “Th1”, which is known to effectively fight the virus, and has little effect on the virus to immunize. It does not belong to the category associated with other types of inflammation that can lead to-mediated pathology. In contrast, severe COVID-19 cases are characterized by uncontrolled inflammation and tissue damage, which helps explain patient recovery.

Second, the CD4 + T cells in the sample are mostly “memory” and “helper” T cells, which stimulate the production of pathogen-specific antibodies. SARS-CoV-2 specific helper T cells found in convalescent patients probably helped initiate effective and specific antibody protection against the virus.

Third, patient CD8 + T cells belonged to a subcategory known to protect against a variety of other viruses. Roan and her group speculate that these cells are toxic to infected cells, are long-lived, and can grow rapidly. This will effectively eliminate SARS-CoV-2 infected cells and prevent virus accumulation after infection.

Interestingly, the majority of T cells specific for SARS-CoV-2 carried surface proteins known to mark long-lived T cells. In fact, these cells were found in convalescent patients more than 2 months after infection. Roan’s team cultured these cells in the presence of common T cell growth factors, which are being tested as a way to improve clinical outcome in COVID-19 patients who are currently T cell depleted. The cells are markedly expanded and show a strong capacity to proliferate.

“These results suggest that SARS-CoV-2-specific T cells are not only long-lived but can be maintained by constant proliferation, so new infections may persist even after the initial infection has resolved. You can repel it.”

To understand why people respond differently to SARS-CoV-2 infections, a study with a large number of patients, including those with severe illness, is needed. Roan and her team have already started comparing T-cell responses in mild and severe cases, investigating how previous exposure to other coronaviruses could boost human immune responses to the new virus. To do.

On the other hand, the features shared by these nine recovered patients provide important insights.

“Our findings show that antibodies to SARS-CoV-2 may decline relatively quickly, but long-term immunity Virus “It can be generated in the form of memory responses, including memory T cells,” Roan says. Lifetime multifunction T cell For SARS-CoV-2. ”