- Email: [email protected]
A tribute to Charles A. Janeway, Jr.
Microbes and Infection 5 (2003) 1285–1286 www.elsevier.com/locate/micinf
Tribute
A tribute to Charles A. Janeway, Jr. (Boston, 1943–New Haven, 2003) Christophe Viret * Inserm Unit 548 and CEA-DRDC, Commissariat à l’Energie Atomique, 17, rue des Martyrs, 38054 Grenoble cedex 9, France Charles Alderson Janeway, Jr., professor of immunobiology at Yale University Medical School, investigator at the Howard Hughes Medical Institute (HHMI) and member of the National Academy of Sciences, died on 12 April 2003 of cancer in New Haven, Connecticut
Over the years I spent working with Charlie as an HHMI postdoctoral fellow and eventually as an Associate, Research Scientist at the Yale University Section of Immunobiology, I learned to know him as the well-respected scientist everybody acknowledges but also as a remarkably generous and open-minded individual. Charlie had been a medicinecommitted student who later switched to basic science. His background was, therefore, a mixture of medical training acquired in New England and of laboratory research conducted both in Europe and in the US. During the 1998 presidential address to the American Association of Immunologists in San Francisco, Charlie emphasized how much his successive research mentors (Hugh McDevitt, John Humphrey, Robin Coombs, William Paul and Hans Wigzell) deeply influenced his approach to science. In the late 1970s, Charlie joined the faculty at Yale University, where he spent his entire academic career as an HHMI appointee. At the time, basic immunology research at Yale was conducted in the Department of Pathology, in a division headed by Richard K. Gershon, with whom Charlie became a close friend. Ironically, Dick Gershon (1932–1983), one of the discoverers of the capacity of T lymphocytes to negatively regulate adaptive immune responses, also died of cancer. Until last year, Charlie honored his memory each year by introducing the Gershon Memorial lecture at the Yale Medical School. In 1988, Charlie was one of the founding members of the now well-established Section of Immunobiology at Yale University School of Medicine. He authored hundreds of scientific publications and is the main author of a famous immunology textbook. He received numerous awards and distinctions and served on the boards of several prominent research institutes and prestigious journals. Charlie trained undergraduate students, graduate students and post-doctoral fellows of many different nationalities. He * Tel.: +33-4-38-78-54-53. E-mail address: [email protected] (C. Viret). doi:10.1016/j.micinf.2003.09.003
also welcomed visiting investigators and clinicians in his laboratory. At the 10-year anniversary of the Yale Section of Immunobiology, which was celebrated in New Haven in October 1999, one could only be impressed by the number of speakers that had trained in Charlie’s laboratory and are now well-respected scientists: E. Dzierzak, S. Porcelli, Y. Liu, J. Kaye, A. Rudensky, to name just a few. It is worth emphasizing that Charlie always enjoyed joining European immunology meetings and accepted numerous invitations for seminars in European education/research institutions. He genuinely loved Europe, particularly the northern part, as well as England. Many of his trainees are now senior scientists in research institutions all over Europe, and both he and his wife, Kim Bottomly, published numerous research articles in European journals. Charlie’s interests were always broad: he contributed to our understanding of many immunological questions such as T/B cell cooperation; the function of CD4/CD8 molecules, for which he proposed the term coreceptor; the definition and analysis of bacterial and retroviral proteins known as superantigens; the differential sensitivity of T lymphocytes to antigen receptor-mediated stimulation, depending on their maturation stage; the intrathymic development of conventional ab T cells; the principles governing the fine interaction of ab T cell receptors with their cognate peptide:MHC complex ligands; the biology of unusual T lymphocytes present in mucosal tissues; and the important role of self determinants’ recognition in selecting and maintaining the mature repertoire of naive CD4 T lymphocytes. Less known and appreciated is his work on idiotypic interaction between B and T cell receptors; together with Kim Bottomly, he helped to describe distinct types of T cell–B cell interaction mediated by direct receptor–receptor interaction. While recognizing that such interactions are unlikely to mediate direct mutual stimulation of B/T lymphocyte responses in a physiological setting, he proposed that they may well play a regulatory role.
1286
C. Viret / Microbes and Infection 5 (2003) 1285–1286
Charles A. Janeway, Jr. (Boston, 1943–New Haven, 2003), professor of immunobiology at Yale University Medical School, investigator at the HHMI, and member of the National Academy of Sciences, was also an eminent member of the editorial board of Microbes and Infection.
One of Charlie’s major achievements remains his proposal that the recognition of conserved microbial molecular motifs by invariant, germ-line-encoded receptors mediates immediate host defense and, in higher vertebrates, instructs lymphocytes with clonally distributed receptors to become activated through the induction of costimulatory signals on cells that also present antigens. Thus, Charlie argued that the immune system evolved to discriminate infectious non-self from noninfectious self and that the two-signal theory of lymphocyte activation is the best theory for such discrimination. Perhaps this concept was best formulated in his introductory lecture at the 1989 Cold Spring Harbor Symposium on quantitative biology on the subject of immune recognition. In fact, we now know of many invariant receptors able to signal antigenpresenting cells such as dendritic cells to express high amounts of costimulatory molecules and secrete cytokines in
response to microbial products. We also know that adaptive immunity is severely compromised in mutant mice in which the signaling pathways normally triggered by such invariant receptors are deficient. Finally, it is worth emphasizing that along with his fundamental immunology work mentioned above, Charlie always maintained a genuine interest in immunological questions with clinical relevance. Animal models for proinflammatory autoimmune disorders such as multiple sclerosis and autoimmune insulin-dependent diabetes mellitus have been the subjects of intense investigations for many years in his laboratory. The deleterious effect of Fas–FasL interaction on pancreatic b cell persistence, the importance of CD8 T cells in the pathogenesis of type I diabetes in NOD mice, and the possibility of controlling experimental autoimmune encephalomyelitis by T suppressor cells induced upon epicutaneous immunization with autoantigens of the central nervous system are a few examples of original contributions to the field of autoimmunity. Charlie developed tight interactions with many colleagues from the Departments of Pathology, Rheumatology and Endocrinology to foster an active autoimmunity research network at Yale, and he was also an assiduous member of the Yale Cancer Center. Not surprisingly, many past members of the Janeway laboratory were medical students, had a medical background or pursued clinical activities. Besides his unique ability to put observations in perspective, his broad knowledge of immunology and his numerous contributions to our understanding of the immune system in particular and to biology in general, there were other remarkable things about Charlie. For instance, Charlie sincerely believed that research should be conducted openly, with a collaborative rather than competitive approach. Cooperation has indeed been a strong tradition in immunology research at Yale since Dick Gershon. Charlie was generous in sharing information and reagents with colleagues, including those outside Yale and overseas. He very often divulged observations long before publication. Charlie’s collaborators enjoyed unusual scientific freedom: he was convinced that excessive supervision is counterproductive, and he always encouraged his students and postdocs to express and test their own ideas. We will certainly miss Charlie for attitudes such as these, as well as for his purely scientific dimension.
Tribute
A tribute to Charles A. Janeway, Jr. (Boston, 1943–New Haven, 2003) Christophe Viret * Inserm Unit 548 and CEA-DRDC, Commissariat à l’Energie Atomique, 17, rue des Martyrs, 38054 Grenoble cedex 9, France Charles Alderson Janeway, Jr., professor of immunobiology at Yale University Medical School, investigator at the Howard Hughes Medical Institute (HHMI) and member of the National Academy of Sciences, died on 12 April 2003 of cancer in New Haven, Connecticut
Over the years I spent working with Charlie as an HHMI postdoctoral fellow and eventually as an Associate, Research Scientist at the Yale University Section of Immunobiology, I learned to know him as the well-respected scientist everybody acknowledges but also as a remarkably generous and open-minded individual. Charlie had been a medicinecommitted student who later switched to basic science. His background was, therefore, a mixture of medical training acquired in New England and of laboratory research conducted both in Europe and in the US. During the 1998 presidential address to the American Association of Immunologists in San Francisco, Charlie emphasized how much his successive research mentors (Hugh McDevitt, John Humphrey, Robin Coombs, William Paul and Hans Wigzell) deeply influenced his approach to science. In the late 1970s, Charlie joined the faculty at Yale University, where he spent his entire academic career as an HHMI appointee. At the time, basic immunology research at Yale was conducted in the Department of Pathology, in a division headed by Richard K. Gershon, with whom Charlie became a close friend. Ironically, Dick Gershon (1932–1983), one of the discoverers of the capacity of T lymphocytes to negatively regulate adaptive immune responses, also died of cancer. Until last year, Charlie honored his memory each year by introducing the Gershon Memorial lecture at the Yale Medical School. In 1988, Charlie was one of the founding members of the now well-established Section of Immunobiology at Yale University School of Medicine. He authored hundreds of scientific publications and is the main author of a famous immunology textbook. He received numerous awards and distinctions and served on the boards of several prominent research institutes and prestigious journals. Charlie trained undergraduate students, graduate students and post-doctoral fellows of many different nationalities. He * Tel.: +33-4-38-78-54-53. E-mail address: [email protected] (C. Viret). doi:10.1016/j.micinf.2003.09.003
also welcomed visiting investigators and clinicians in his laboratory. At the 10-year anniversary of the Yale Section of Immunobiology, which was celebrated in New Haven in October 1999, one could only be impressed by the number of speakers that had trained in Charlie’s laboratory and are now well-respected scientists: E. Dzierzak, S. Porcelli, Y. Liu, J. Kaye, A. Rudensky, to name just a few. It is worth emphasizing that Charlie always enjoyed joining European immunology meetings and accepted numerous invitations for seminars in European education/research institutions. He genuinely loved Europe, particularly the northern part, as well as England. Many of his trainees are now senior scientists in research institutions all over Europe, and both he and his wife, Kim Bottomly, published numerous research articles in European journals. Charlie’s interests were always broad: he contributed to our understanding of many immunological questions such as T/B cell cooperation; the function of CD4/CD8 molecules, for which he proposed the term coreceptor; the definition and analysis of bacterial and retroviral proteins known as superantigens; the differential sensitivity of T lymphocytes to antigen receptor-mediated stimulation, depending on their maturation stage; the intrathymic development of conventional ab T cells; the principles governing the fine interaction of ab T cell receptors with their cognate peptide:MHC complex ligands; the biology of unusual T lymphocytes present in mucosal tissues; and the important role of self determinants’ recognition in selecting and maintaining the mature repertoire of naive CD4 T lymphocytes. Less known and appreciated is his work on idiotypic interaction between B and T cell receptors; together with Kim Bottomly, he helped to describe distinct types of T cell–B cell interaction mediated by direct receptor–receptor interaction. While recognizing that such interactions are unlikely to mediate direct mutual stimulation of B/T lymphocyte responses in a physiological setting, he proposed that they may well play a regulatory role.
1286
C. Viret / Microbes and Infection 5 (2003) 1285–1286
Charles A. Janeway, Jr. (Boston, 1943–New Haven, 2003), professor of immunobiology at Yale University Medical School, investigator at the HHMI, and member of the National Academy of Sciences, was also an eminent member of the editorial board of Microbes and Infection.
One of Charlie’s major achievements remains his proposal that the recognition of conserved microbial molecular motifs by invariant, germ-line-encoded receptors mediates immediate host defense and, in higher vertebrates, instructs lymphocytes with clonally distributed receptors to become activated through the induction of costimulatory signals on cells that also present antigens. Thus, Charlie argued that the immune system evolved to discriminate infectious non-self from noninfectious self and that the two-signal theory of lymphocyte activation is the best theory for such discrimination. Perhaps this concept was best formulated in his introductory lecture at the 1989 Cold Spring Harbor Symposium on quantitative biology on the subject of immune recognition. In fact, we now know of many invariant receptors able to signal antigenpresenting cells such as dendritic cells to express high amounts of costimulatory molecules and secrete cytokines in
response to microbial products. We also know that adaptive immunity is severely compromised in mutant mice in which the signaling pathways normally triggered by such invariant receptors are deficient. Finally, it is worth emphasizing that along with his fundamental immunology work mentioned above, Charlie always maintained a genuine interest in immunological questions with clinical relevance. Animal models for proinflammatory autoimmune disorders such as multiple sclerosis and autoimmune insulin-dependent diabetes mellitus have been the subjects of intense investigations for many years in his laboratory. The deleterious effect of Fas–FasL interaction on pancreatic b cell persistence, the importance of CD8 T cells in the pathogenesis of type I diabetes in NOD mice, and the possibility of controlling experimental autoimmune encephalomyelitis by T suppressor cells induced upon epicutaneous immunization with autoantigens of the central nervous system are a few examples of original contributions to the field of autoimmunity. Charlie developed tight interactions with many colleagues from the Departments of Pathology, Rheumatology and Endocrinology to foster an active autoimmunity research network at Yale, and he was also an assiduous member of the Yale Cancer Center. Not surprisingly, many past members of the Janeway laboratory were medical students, had a medical background or pursued clinical activities. Besides his unique ability to put observations in perspective, his broad knowledge of immunology and his numerous contributions to our understanding of the immune system in particular and to biology in general, there were other remarkable things about Charlie. For instance, Charlie sincerely believed that research should be conducted openly, with a collaborative rather than competitive approach. Cooperation has indeed been a strong tradition in immunology research at Yale since Dick Gershon. Charlie was generous in sharing information and reagents with colleagues, including those outside Yale and overseas. He very often divulged observations long before publication. Charlie’s collaborators enjoyed unusual scientific freedom: he was convinced that excessive supervision is counterproductive, and he always encouraged his students and postdocs to express and test their own ideas. We will certainly miss Charlie for attitudes such as these, as well as for his purely scientific dimension.