Hidden strength behind a fever: Research shows how T-cells can ‘supercharge’ body

Rosemary Jackson knows all too well the horrors of life-threatening diseases such as malaria. 

The former student at Gisborne’s Campion College contracted it after volunteer work turned into a deadly civil war experience in the volatile African nation of South Sudan — one of the most dangerous countries in the world. 

Now doing infection research as she works toward a PhD, Jackson vividly recalls what her body went through in the throes of the mosquito-borne disease in the Third World country. 

Every inch of her body was aching. She was delirious and nauseous. The arid, sub-Saharan air stoked the scorching heat of her body. She remembers lying face down on a mercifully cool slab of concrete, pleading for the heat and pain to leave her body. 

To make things worse, she had minimal access to medical care, her only relief from the sustained fever and pain coming from paracetamol and ibuprofen. 

Jackson, in her early 20s, had gone to the city of Yei — located near the borders of the Democratic Republic of Congo and Uganda — to volunteer at a children’s home. 

However, after a few months, she suddenly found herself in the middle of a civil war, caring for 130 children. 

With mass evacuations under way, medical care in the city became almost non-existent, and basics like food and fuel were scarce. 

Jackson was forced to step up to a medical role, dressing wounds and treating infections on a daily basis under the supervision of two American nurses. 

During her 18 months there, she contracted malaria three times. 

Jackson is back in New Zealand where she is undertaking her PhD in the Gasser Laboratory at the Malaghan Institute, supervised by Dr David O’Sullivan. 

The Malaghan Institute is an independent biomedical research charity with a focus on breakthrough discoveries in immunology and immunotherapy. 

Jackson is investigating if a mild to moderate fever helps T-cells mount a stronger attack against infections. Specifically, she is looking into how T-cells change on a molecular level during increased temperatures and how long the fever needs to be sustained to bring about any beneficial changes in the T-cells. 

“Fever happens when our immune system detects a threat and communicates the presence of an infection to our brains. Our body’s thermostat, located in part of our brain called the hypothalamus, then turns up the heat,” she says. 

“Our body’s average temperature is about 37C. This increases to 38C for a low-grade fever and up to 41C for a high-grade fever. Maintaining this higher temperature takes a huge amount of energy and is very taxing on the body. As most of us have experienced, this feels miserable. Fever can bring about crippling fatigue that leaves you unable to carry out your daily functions, along with body aches and loss of appetite. Paradoxically, fever also makes us feel like we’re cold — making us seek the warmth of blankets and heaters.” 

This physiological response is common across all mammals. Even cold-blooded animals such as fish and reptiles will seek out warmth during infections to raise their body temperature. This indicates that a higher temperature may be beneficial to the body in some way during infection. 

“Everyone has heard grandma’s advice to ‘let the fever run its course’, that an increased body  ... [temperature] will drive out whatever is infecting the body,” Jackson says. 

“What if that wasn’t entirely unhelpful advice? In our modern lives, we tend to run away from any uncomfortable experience. We tend to think of fever as being a product of the infection, rather than our body’s own way of launching an attack against the infection.” 

Fevers can create a hostile environment and inhibit the growth of infectious agents such as invading bacteria and viruses which are adapted to normal human body temperature. 

“What is less known is how fevers also serve to aid our body’s offensive strategy against the infectious agent. Some evidence suggests the increased temperature results in enhanced immune function, helping white blood cells, including T-cells, kick into gear to overcome the infection. 

“T-cells are some of our most important immune cells. Part of their response involves a rapid expansion phase where one highly specialised T-cell will become activated and multiply to produce a whole army of clones that can target and kill the specific threat. 

“For this rapid expansion of immune cells to occur, the body needs an increase in both energy and building materials for those new cells. It’s possible that elevated temperatures help the T-cells to do this more effectively, ‘supercharging’ them from the inside.” 

Jackson is conducting experiments in which she takes T-cells and activates them at either normal temperature (37C) or moderate fever temperature (39C) and leaves them overnight. This mimics common patterns where an individual gets sick in the evening and has a fever overnight, which then subsides in the morning. 

She then monitors the cellular and molecular changes that occur over the next several days in both these sets of T-cells to understand if there is any difference in the cells which were activated at fever temperatures. 

“So far, we’ve found some very interesting results. T-cells that were exposed to fever-like temperatures for several hours when activated, along with their subsequent generations of clones, showed increased immune activity even several days after being returned to normal body temperature. 

“In contrast, T-cells kept at normal body temperature from the start did not show this same heightened activity. This suggests that even a brief period of increased temperature triggered signals within the cells that were passed down to their clones, instructing those clones to become more potent in their immune response.” 

She will soon begin studying these effects in infectious disease models, including influenza, to see how these molecular changes in T-cells may alter the immune response during infection.