Regulatory T cells play a vital role in managing autoimmune diseases and cancer. This year, the scientists who discovered these cells were honored with the Nobel Prize in Medicine.
The human immune system consists of approximately 1.8 trillion cells, which spring into action to combat infections. This vast army includes macrophages, neutrophils, natural killer (NK) cells, T lymphocytes, and B lymphocytes, collectively weighing around 1.2 kilograms, similar to the weight of a liver.
Within this complex defense system are specialized white blood cells designed to regulate immune responses. Sometimes, the immune system can mistakenly attack the body”s own tissues, leading to autoimmune diseases. This is where regulatory T cells come into play. “They act as peacekeepers that temper our immune reactions,” explains Dr. María Mittelbrunn, a scientist at the Severo Ochoa Molecular Biology Center.
Conversely, the immune system can also fail to detect harmful invaders, such as cancer cells, which can evade elimination. Discovered in 1995, the significance of regulatory T cells has been recognized internationally, leading to the recent Nobel Prize awarded to their discoverers: Shimon Sakaguchi from Japan and Americans Mary E. Brunkon and Fred Ramsdell.
When a pathogen, such as a virus, bacteria, or fungus, breaches our initial defenses (the skin and mucous membranes), the body activates its immediate immune response. “All organisms have this fundamental response, which reacts similarly to any threat by recognizing common patterns,” says the immunologist. Initially, macrophages and neutrophils are the primary responders, engulfing or destroying the invaders.
As the situation escalates, if this initial response proves insufficient, the immune system engages its adaptive response, which is unique to vertebrates. This more precise response is tailored to specific pathogens and takes about six days to develop, forming the basis for all vaccines. The key players in this adaptive response are the B and T lymphocytes.
B lymphocytes, produced in the bone marrow, generate antibodies designed to attach to pathogens (technically known as antigens, which are substances that provoke immune responses). These antibodies can neutralize pathogens directly or flag them for destruction by macrophages or neutrophils.
T lymphocyte precursors also originate in the bone marrow but migrate to the thymus—a gland located behind the sternum—to mature. “It is like a school where they learn their functions,” explains Mittelbrunn. Their precision stems from their ability to recognize specific characteristics of invaders (peptides) and the random generation of various combinations to target even unknown pathogens. Of this vast array, 99% are eliminated to avoid harming the body, making this aspect of immunology quite complex.
Within T lymphocytes, there are two main types: helper T cells (CD4) that orchestrate immune responses and assist B cells in producing antibodies, and cytotoxic T cells (CD8) that are equipped to eliminate infected or cancerous cells.
All these components coordinate during an infection. The innate response is triggered, activating B lymphocytes, T lymphocytes, and cytotoxic T cells, resulting in a fierce battle among these cells. It is during this tumult that regulatory T cells (a subtype of CD4) emerge. “Their role is to calm everything down and suppress the inflammatory response. They effectively tell the immune “police” to stand down, as the threat has been neutralized, restoring order,” says Mittelbrunn.
Once the conflict is resolved, most of these immune specialists perish, leaving a small fraction as memory cells to effectively combat future infections from the same pathogen. The balance maintained by regulatory T cells is crucial for overall health. If they fail to regulate immune responses, the system may attack the body”s own tissues, leading to autoimmune diseases. Conversely, if their regulation is inadequate, cancer cells may evade detection and thrive. “This is a very delicate balance,” concludes Mittelbrunn.
