The future of immunity is
in T cell mitochondria

For more than four decades, Brigitte König, Ph.D. has been exploring the characteristics of the human immune system—both its defenders and its attackers. As a professor in the special field of medical microbiology and infection immunology at the Institute for Medical Microbiology and Virology at the University of Leipzig - and collector of rare flowers - König began her career with research into allergies. But she soon pursued viral infections, especially of the respiratory tract. Cystic fibrosis, sepsis, Epstein-Barr and a host of other infectious diseases eventually became part of her wide-ranging immunological research.
  
“I regularly work in interdisciplinary forms, from the cell to the microorganism to the organs to the whole body,” says König, who in her spare time likes to bike and take in nature. “It is fascinating to combine these fields. This is what I really, really like.” 

One of the aspects that fascinates König the most is the T cell, a type of white blood cell that belongs to the adaptive immune system, which identifies and targets specific invaders within cells. The T cell communicates with the innate immune system, which is the first line of the body’s defense, with a one-size-fits-all approach to battling foreign entities both inside and outside the body. “T cells get signals from the innate immune system, but they also give signals to the innate immune system,” says König. 

In recent years, the T cell has been widely implicated in the regulation of the entire immune system. And without healthy T cells the immune system is doomed to fail.

T cells vs antibodies

Antibodies are known as the first line of viral defense working to block a virus from infecting a cell. But antibodies can be evaded when viruses mutate (and antibodies can dissipate with time). The most recent example being from COVID-19 variants – such as Omicron – known to not always elicit a reaction from antibodies. But if this is the case why are some infected individuals getting seriously ill? The answer may be in their T cells.  

A strong T-cell response is essential to a wide variety of immune functions, including defense against viral infections, vaccine effectiveness, autoimmune disease and healthy aging. “Without good T cells, you get allergies, you get autoimmune disease, your vaccination is not successful, and you can’t combat microorganisms like tuberculosis,” she says. 

König approaches the study of T cells from multiple angles. At Magdeburg Molecular Detection, a molecular research, testing and diagnostic company she founded, her team has been monitoring the T-cell responses of patients based on samples, taken from about 4,000 people so far, who have an infection of some kind, including SARS-CoV-2. 

“If you have to handle 200–300 samples in one day, you must look for reliable assays that with very fast results. QIAGEN’s was the ideal one,” she says. “We can assay several hundreds a day and get really good results.” 

In December 2021, as Omicron variant cases were exploding, “we wanted to research a T-cell test on people facing vaccination choices: People who wanted to find out whether they are already infected, whether they are protected, or whether they should be vaccinated quickly,” she says. 

The test they used was QIAGEN’s QuantiFERON SARS-CoV-2 RUO assay, which provides qualitative detection of IFN-gamma produced by CD4+ and CD8+ T-cell responses to SARS-CoV-2 peptides.

T cells and vaccine response

König monitors the T-cell response from people who have been vaccinated against COVID-19. “It’s very important to see how they are protected—whether the T-cell response is very broad against all the parts of the virus or only a very small part of the virus,” she notes. 

They’ve used the QIAGEN QuantiFERON SARS-CoV-2 Extended Set kit for this part of the analysis: “It is very important to cover all the epitopes of the SARS-CoV-2 virus,” she says. 

“T cells play a very important role in vaccine development,” König says. “Most viruses are defended best with T cells. It’s important that you develop a vaccine that activates the T-cell response to be really successful. The T-cell response should be incorporated into vaccination strategies and monitored before vaccination. The immune system is very complex and individual, so vaccination should also be an individualized procedure—not one size fits all.” 

The results have been intriguing. “We are learning a lot with every sample. We’re seeing that people who are infected really developed a very good T-cell response, but it might disappear from the blood after six to twelve months,” she says. “We also see a very good correlation between T-cell response and how ill people are. The people who are very ill have a much stronger T-cell response than people who are slightly infected.” 

They’re also finding that “after vaccination, only a few people develop a really good T-cell response,” König notes. Which begs the question: Why?

The role of mitochondria in healthy T cells

T cells are important in keeping a body healthy. But what maintains the T cells? König is probing the relationship between T cells and mitochondria. Mitochondria don’t just provide energy to each cell, but also mediate the development, metabolism, and activation of T cells. So T cells only perform well if their cellular power sources are functioning. 

König sees a bright future ahead for mitochondrial medicine, including mitochondrial transfer in stem cell and anti-cancer therapy. T cells will be key. “For immunotherapy, you need T cells which respond really well. And if the T cells have bad mitochondria, then the immunotherapy will not function.” 

“It's called immune metabolism,” König says. “Mitochondria is central to everything. Where I look to see if the T cells are responding well is the gamma interferon response, which is one of the most important cytokines or mediators. And we monitor mitochondrial function through oxygen consumption and the production of  protons.” 

They also monitor the buildup of senescent cells, which are cells that have stopped dividing but resist removal by immune cells like T cells. This buildup “is very dangerous, because they promote rapid aging through chronic infection, chronic diseases or chronic inflammation,” König says. T cells with mitochondrial dysfunction especially can’t keep up with the burden of their removal.  

“Mitochondria also have their own DNA,” she notes. “We have already started to sequence the whole mitochondrial DNA and to develop bioinformatic tools to see the quality of the mitochondria in each person or in each T cell.” 

The goal of this research is to optimize vaccine development and also healthy aging at every stage of life, from newborn to elderly.  The goal is a lofty one. “We want to prolong healthy aging until 120 years, ideally,” she says. But that is only possible with healthy T cells.