September 29, 2020

much more than antibodies in immunity against COVID-19

Lately the focus of experts studying the pandemic has been pointing to T cells. What are they and why are they so important for COVID-19?

T cells are lymphocytes, white blood cells that mature in the thymus, an organ located under the breastbone. They develop from birth to 25 years of age, and circulate through the blood and lymph in the form of “naive” T cells (so called because they have never fought against a pathogen), each of them being specific against an infectious organism.

As we explained in a previous articleWhen the body is first attacked by a pathogen, an innate immune response first appears. If it is not enough to eliminate the pathogen, traces of it accumulate in the lymph nodes and the spleen. The thing is not there, because these remains activate “naive” T cells of the adaptive immune system, which arrive through the lymph and recognize it. When activated, they immediately become “effector” T cells. And they start the fight.

The interesting thing is that, once they have eliminated the pathogen, most of the effector cells die, but some transform into “memory” T cells and persist in the body. Memory T cells, if generated, are able to migrate to the body’s organs and stay there for a long time (“resident” memory T cells), in addition to circulating in lymph and blood.

The advantage is that, if the same pathogen happens to attack the organism a second time, the resident T cells immediately mount an immune response, alert the innate immune system and start the production of antibodies.

In this case, the process of eliminating the pathogen, if the organism has a good memory of a previous infection, is much faster and usually lasts at most 7 days (compared to 14 in the first “attack”). The reason is that you no longer need to start with the innate response. Also, memory T cells do not need to pass through the lymph nodes or spleen, but can respond immediately. Therefore, an ideal vaccine should generate memory T cells, in addition to antibodies.

Can we be protected from the virus without having antibodies?

To find out if someone has or has had the COVID-19 disease, two methods are used, PCR and serological tests, which detect genetic material of the virus and antibodies, respectively. In the case of COVID-19, as antibodies decline rapidly, T cells would today be the best candidates to speak of long-lasting protection.

Performing a PCR or serological test is simple and can be done outside of a hospital. However, a test for specific T cells for a pathogen is complicated, more expensive. What’s more, so far it is only performed in research centers and hospitals.

This complicates the situation because the question arises as to whether people who have had the disease and have lost antibodies (or even never had them) can present immunity against the virus in the form of memory T cells. For example, memory T cells from previous colds they can react against the SARS-CoV-2 virus. There are also examples of people who have been infected and no antibodies. As a result, more and more attention is being paid to T cells in COVID-19 vaccine trials.

What do vaccine trials say about T cells?

There are two important reasons for studying T cells in vaccine trials. The first, as we have explained, to see if there is lasting memory. The second is to ensure that the vaccine will not produce harmful effects. In this regard, T cells originate two types of response: Th1 (which does not have counterproductive effects) and Th2 (which can produce them by inducing exacerbated inflammatory response, as seen with previous respiratory viruses).

The presence of T cells and the type of response they produce is studied by analyzing the levels of the defending substances they secrete in the blood. Namely: interferon gamma (IFN-gamma) and interleukin 2 (IL-2), in the case of the Th1 response; and the interleukins IL-4, IL-5 and IL-13, in the case of the Th2 response.

Vaccines will be more effective if, in addition to causing the manufacture of antibodies (humoral response), they are capable of increasing the levels of our memory-developing T cells (cellular response). The following table details the detection of T cells in the preclinical phase trials (macaques) and in the successive clinical phases of the vaccines in development against COVID-19.

The Conversation

We need to study T cells in both vaccines and COVID-19 monitoring

The bottom line is that it is not enough to study antibody levels to know if a person is immune to the virus. It is also necessary to study if your T cells react against it in an effective and lasting way, that is, if you have memory T cells. Therefore, it would be worth designing a simpler system to study T cells from people who are thought to have passed the disease but do not have antibodies.

Regarding vaccines, we know that in tests with macaques vaccinated against COVID-19, virus-specific T cells are observed up to 4 weeks after being infected with it. The data is encouraging, since it accounts for its effectiveness. But from now on it will also be important to check if these cells remain after 6 months or a year.

Performing these same studies in clinical phases will take longer. But if they are positive, we can think that in humans these vaccines will generate a lasting immune response, regardless of the levels of antibodies, thanks to the presence of T cells.

Matilde Cañelles López is iScientific researcher at the Center for Human and Social Sciences (CCHS – CSIC) and Maria Mercedes Jimenez Sarmiento is cTenured scientist in Systems Biochemistry of the bacterial division and scientific communicator at the Margarita Salas Biological Research Center (CIB – CSIC).

This article was originally published on The Conversation. You can read it here.


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