Obituary: Thomas Fletcher Tedder, PhD (1956–2024)

Thomas F. Tedder, PhD (1956-2024) Thomas F. Tedder (Tom) passed away on March 18, 2024 after a long health battle, surrounded by family and loved ones. Tom was the Alter E. Geller Distinguished Professor for Research in Immunology in the Duke University School of Medicine, where he devoted 30 years as a faculty member and professor. He was an outstanding American immunologist of international repute, particularly for his work on B cell biology and regulation. He left behind a loving family, notable accomplishments, and an international community of colleagues, collaborators, trainees, and admirers. According to the biography described in his review 1) and other sources, he was born in Chateauroux, France on May 14, 1956 and grew up in Fort Walton Beach, Florida. He entered graduate school at the University of Alabama at Birmingham under the tutelage of Max Cooperand received his PhD in 1984. Tom's goal was to develop reagents to identify human B cell subsets and their differentiation stages, and he investigated a series of B cell surface molecules (now known as CD21, CD24, and CD45RB) that could potentially regulate B cell function and produced monoclonal antibodies (mAbs) that react specifically with them. The concept was to identify on/off molecular switches for the treatment of B-cell malignancies, immunodeficiency, and autoimmune diseases. From 1985 to 1998, Tom worked as a faculty member in Stuart Schlossman's laboratory in the Department of Tumor Immunology at the Dana-Farber Cancer Institute and Harvard Medical School. Lee Nadler and other members of the department were also developing mAbs against B cell surface molecules with the common goal of elucidating the function of each target molecule. During that period, Tom and his collaborators not only identified new molecules such as CD19, CD20, CD21, and CD22, but also clarified their biochemical characteristics, interactions, and in vitro functions. In addition to B cell surface molecules, he also identified molecules with unique functions such as L-selectin and CD83. In 1993, he became the founding chairman of the newly established Department of Immunology at Duke University Medical Center, a position he held until 2010. He was an enduring leader, innovator and mentor in all aspects and expanded the department's research areas to cover a wide range of topics in immunology. His own research shifted from studies of human B cell development to studies of mouse models, where he would be able conduct experiments more efficiently and expediently. He created a series of knockout and transgenic mice for the genes encoding the molecules he had been studying, and clarified one after another how these molecules worked in vivo. He continued to examine how B lymphocyte cell surface molecules regulate innate and adaptive immunity. Finally, sufficient knowledge of the functions of CD19, CD20, CD22, and others was obtained to provide feedback to humans on mAbs with the potential for new therapeutic approaches in oncology and autoimmune diseases. In addition to B cells, Tom continued his excellent work on L-selectin and other adhesion molecules and CD83 expressed on mature dendritic cells. Tom made several breakthroughs in his research on regulatory B cells. In the early 2000's, B cells were thought to act only to produce antibodies or enhance inflammatory immune responses. However, Tom identified a unique regulatory B cell subset that suppress inflammation, innate immunity, adaptive immunity, and autoimmunity; a rare but specific subset of regulatory B cell is functionally characterized by their ability to produce IL-10, a potent regulatory cytokine in both human and mice. This regulatory B cell subset was named B10 cells as its function entirely depends on IL-10. Development, phenotype, and effector functions of B10 cells and other regulatory B cells, as well as mechanism demonstrating their functional importance in inflammation, immune responses, and autoimmune diseases are ongoing and are expanding research fields around the world. Tom has at least 412 total publications including three "Nature " papers and three "Cell" papers, and 25 issued patents related to CD19, CD20, CD22, CD83, and L-selectin amongst others. He has founded four biotherapeutic companies, Cellective Therapeutics, Angelica Therapeutics, Cellective BioTherapy and most recently, Antigenomycs. Notably, Tom developed inebilizumab, a monoclonal antibody against human CD19, at Cellective Therapeutics, which has shown overwhelming efficacy in the treatment of the refractory autoimmune disease "neuromyelitis optica spectrum disorders" and is widely used worldwide under the brand name Uplizna. Tom's contributions to dermatology and dermatologists, especially in Japan, have been very significant. Shinichi Sato was the first dermatologist and the first Japanese to become a member of Tedder's lab. Shinichi and Manabu Fujimoto, and other dermatologists, achieved great results there which earned Tom's strong trust, and a deep bond was formed between Tom's laboratory and the Japanese dermatological community. In total, 17 Japanese dermatologists belonged to Tom's laboratory and the 7 authors of this article have become professors of dermatology in Japan. In addition, many dermatologists have conducted research in Japan using genetically engineered mice and antibodies obtained from Tom, and many have obtained degrees and published papers with his guidance. Japanese dermatologists have co-authored more than 100 papers with Tom. He visited Japan more than five times to give lectures at academic conferences and to spend time with his Japanese colleagues for whom he cared deeply. He has truly contributed to the development of not only immunology, oncology, and rheumatology, but also dermatology all over the world. Tom was always stylish, smartly cool, and a gentleman. The way he walked was impressive, staring straight ahead and walking with strong intention. It seemed to reflect his way of life, which was to move forward steadily, step by step, toward his goal. "What's new? "Tom often said to us when we crossed paths in the lab or in the hallways. In his case, the question was of course always about research. We'd often hesitate to respond because we did not always have new and good experimental data. Whenever Tom saw interesting data, he would think with a pure, boyish gaze and come up with great ideas for how to further explore this data. Following his attitude, we will always be on the lookout for new discoveries in our daily clinical practice, research, and life. He will be forever cherished and deeply missed by the researchers, students, and others with whom he interacted or shared his knowledge, as well as by huge numbers of patients and their families who were saved by his research. 1LeBien T.W. Tedder T.F. B lymphocytes: how they develop and function.Blood. 2008; 112: 1570-1580Crossref PubMed Scopus (875) Google Scholar