Coronavirus: T cells in patients missing antibodies

Our own immune systems follow the pattern outlined by Mithridates. If you expose yourself to a small amount of the toxin, or pathogen, you develop some amount of resistance to it. Adrienne Mayor...#

Adrienne - You can actually stimulate the immune response by taking small amounts of allergens, for instance, that's what doctors recommend to avoid peanut allergies - that small amounts of peanuts are given to children. A similar response works with insect stings, and a variety of different poisons and toxins.

This is crucial during the pandemic, as scientists are trying to understand how good different people’s immune systems are at mounting a resistance to the coronavirus, and whether a successful vaccine is possible. And there’s been evidence for a while now that people who get exposed to low doses of the virus, who haven’t made antibodies to it, have still developed some resistance in the form of immune cells called T cells. That evidence comes from the Karolinska Institute in Sweden, and from researcher Hans-Gustaf Ljunggren…

Hans-Gustaf - T cells are a type of white blood cell. Their function is to recognise virus-infected cells and other types of aberrant cells, and essentially kill them off. Until our paper that had only been very few scattered reports on T cell responses. And we set out to carry out an extensive investigation into the T cell response in the course of COVID-19.

Phil - And what did you find?

Hans-Gustaf - We found that individuals with mild symptoms, or even asymptomatic individuals, that had been living together with infected individuals with symptoms, had developed T cell responses to the virus. Not all of them, but most of them had.

Phil - Were they then immune to the coronavirus?

Hans-Gustaf - That is a difficult question. We don't know. Immunity to us immunologists is kind of relative. They certainly have generated a response towards the virus. If it will fully protect them, we don't know.

Phil - Why had no one noticed this before? Because people made a big deal about antibody tests. Why haven't people been looking into T cells?

Hans-Gustaf - It's fairly easy to develop antibody based assays. It is quite much more complicated to assess for virus specific T cells. It requires, first of all, isolation of cells from patients' blood. It requires specialised laboratories, it requires specialised techniques. While at the same time, you have to take into consideration the fact that we may also have T cell responses to other previous coronavirus infections, some of which may actually partly protect us.

Phil - How do the actual T cell responses though, compared to someone's antibody responses, for example?

Hans-Gustaf - Well, everyone that has mounted an antibody response has also mounted a T cell response. But in addition to that, we identified quite a number of individuals who had not developed antibody responses, but had T cell responses. In fact, when we looked at blood donors in Stockholm, there was a frequency of about 15% of them having antibodies to the viruses. While we found that up to 30% had mounted T cell responses to the virus.

Phil - Was that a surprise to you?

Hans-Gustaf - In part it was a surprise, but at the same time, when you go back to the immunological literature, you may need higher exposure of an antigen, like a virus to mount an antibody response, than a T cell response.

Phil - Can you explain what might be going on in the person's immune system, then?

Hans-Gustaf -  The T cells are recognising infected cells as foreign, and the T cells are actually necessary to stimulate another type of cell called B cells. That is the cell that produces antibodies. It might be so that the response has been sufficiently strong to activate T cells, but not strong to stimulate B cells to the degree that they start to generate antibodies, we speculate. It could of course be so that some antibodies orient rating that we cannot detect.