The 2025 Nobel Prize in Physiology or Medicine recognized the discovery of regulatory T cells, which are immune cells that maintain tolerance and prevent autoimmunity. At Augusta University, scientists have built upon that foundational work, uncovering how these cells function, fail and evolve across diseases like cancer and atherosclerosis.
Regulatory T cells, or Tregs, are essential for controlling immune responses and preventing the body from attacking its own tissues. Early discoveries by Shimon Sakaguchi, MD, PhD, who identified the CD25 marker and later the transcription factor FoxP3, revealed how Tregs suppress immune activation. Sakaguchi, a distinguished professor at Osaka University in Japan, shared the Nobel Prize with Mary E. Brunkow, PhD, Princeton University, and Fred Ramsdell, PhD, University of California, Los Angeles.
Sakaguchi once shared lab space with Nicholas Gascoigne, PhD, now a professor at AU’s Immunology Center of Georgia, where he studies T-cell signaling and differentiation — a connection that ties the global history of Treg research to the university’s ongoing expertise.
Gascoigne’s research continues to illuminate how Tregs differentiate and signal, critical steps in ensuring immune tolerance to self.
“Drs. Sakaguchi, Brunkow and Ramsdell have made enormous contributions to our understanding of how immunological tolerance works, so this prize is very well deserved,” Gascoigne said. “I was happy I could help Drs. Shimon and Noriko Sakaguchi when they needed lab space back in the early ‘90s. They were wonderful to work with.”
At Augusta University, David Munn, MD, co-director of the Pediatric Immunotherapy Program of the Medical College of Georgia at Augusta University, made seminal discoveries showing that Tregs are not always stable.
Munn’s team demonstrated that these cells could lose their suppressive identity and become “exTregs,” adopting pro-inflammatory characteristics under certain conditions. Munn also uncovered an entirely distinct tolerance mechanism through indoleamine 2,3-dioxygenase, a pathway independent of FoxP3 that regulates immune balance through tryptophan metabolism.
“In particular, the work of Shimon Sakaguchi and Fred Ramsdell was profoundly influential on our early work, as we were just starting out to explore how the immune system is regulated in pediatric cancers,” Munn said. “The work of these Nobel laureates helped transform the scientific understanding of how the immune system responds — or fails to respond — in the setting of tumors.”
Catherine “Lynn” Hedrick, PhD, co-director of the Immunology Center of Georgia, further expanded this understanding by showing that Tregs can convert into follicular helper T cells, offering new insight into how immune regulation can shift toward antibody production in chronic inflammatory diseases such as atherosclerosis.
“Understanding how regulatory T cells can shift identities helps explain why the immune system sometimes loses balance in chronic disease,” Hedrick said. “By tracing how Tregs convert into other helper cells, we’re uncovering new therapeutic targets to restore immune harmony in conditions like atherosclerosis.”
Building on these advances, Klaus Ley, MD, co-director of IMMCG, and his team have investigated how exTregs contribute to cardiovascular inflammation, identifying them in human tissues and clarifying their role in atherosclerosis. His lab also recently discovered human exTregs, providing the first direct evidence of these cells in people. Two postdoctoral fellows in Ley’s lab, Qingkang Lyu, PhD, and Smriti Parashar, PhD, continue this work, exploring how regulatory and ex-regulatory T cells influence chronic disease progression.
Additionally, Dimitrios Moskofidis, MD, PhD, a professor based in the Georgia Cancer Center, contributed key early insights into immune tolerance and memory, defining how effector T cells persist or are deleted following infection.
“Together, these discoveries place Augusta University and the Immunology Center of Georgia at the forefront of modern immunology, connecting molecular mechanisms of tolerance to real-world diseases and therapies,” Ley said.
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