Inflammation represents a long-conserved biological process characterized by the release of chemical messengers that regulate the immune response. When the body faces an injury or infection, the inflammatory response signals immune cells and other mediators to go after the insult. Classically, we can recognize four cardinal signs of inflammation: heat, pain, redness, and swelling. Modern research has included loss of function as a fifth symptom associated with inflammation.
In brief, inflammation increases blood flow to a particular area of the body. The associated vessel dilation helps carry heat from the body's core to the inflamed area, often resulting in a fever. In addition to accounting for heat, the increased blood flow can lead to skin reddening. Dilated blood vessels allow for greater permeability, allowing immune cells to flow to the area, causing swelling. Inflammation sensitizes pain mediators, which can increase pain in the area. Loss of function can occur as a result of pain and swelling.
Despite its role in inflammation, the direct impact of fever on immune cells remains ambiguous. T cells, immune cells involved in killing tumor cells, adapt to fever-driven increases in body temperature through an inherent heat-shock response. However, how febrile temperature impacts T cell growth and survival remains unknown.
A recent study in Science Immunology has revealed significant findings on the effects of fever on CD4 T cells, a crucial class of immune cells for effective anti-tumor immunity. The study's main findings include the increased survival and function of CD4 T cells when exposed to febrile temperatures.
The study used mouse immune cells to examine how febrile temperatures affected the survival and function of CD4 T cells. Processes like T cell metabolism, proliferation, and effector activity increased when immune cells were exposed to fever temperatures.
The researchers also investigated the role of regulatory T cells (Tregs), a subset of CD4 T cells that suppress anti-tumor immunity. The study found that under febrile conditions, the immunosuppressive activity of Tregs decreased, suggesting a shift in the balance of immune activity.
In contrast, another subset of CD4 T cells, T helper 1 (TH1) cells. This subset of T cells stimulates other immune cells, including killer T cells, the immune cells responsible for killing cancer cells. When exposed to fever-range temperature, TH1 cells underwent significant mitochondrial stress, resulting in DNA damage. While most of the cells died when subjected to the elevated temperature, the surviving TH1 cells had more mitochondria, the component of the cell responsible for making energy. These TH1 cells also exhibited more efficient immune functions and enhanced activity.
The study's findings have significant implications for cancer treatment. It shows that CD4 T cells, when exposed to fever-range temperatures, become better equipped to respond to an insult, such as cancer. Simultaneously, the activity of immunosuppressive Tregs becomes hindered, suggesting more effective anti-tumor immune responses would result. Furthermore, while most TH1 cells exposed to heat succumb to the stress, the surviving cells adapt by altering their mitochondria and become more efficient at carrying out the immune response.
Sources: J Gerontol A Biol Sci Med Sci, Stat Pearls, J Immunol, Science Immunol