Tim R. Mosmann, Ph.D.

Dr. Mosmann received B.S. degrees in both Chemistry and Physiology, and in Microbiology, from the University of Natal and Rhodes University in South Africa. He subsequently emigrated to Canada and obtained his Ph.D. in Microbiology at the University of British Columbia. Research fellowships at the University of Toronto and University of Glasgow were followed by his appointment as an assistant professor at the University of Alberta. He then spent 8 years in industry, as a research scientist at DNAX Research Institute in Palo Alto, California - prior to rejoining the University of Alberta as Chairman of the Department of Immunology. In 1998, he was recruited to the University of Rochester.

Dr. Mosmann has made many important contributions to the field of Immunology, and is perhaps best known for his discovery, with his colleague Dr. Robert Coffman, of the TH1 and TH2 subsets of T lymphocytes, which determine whether the host response to infection will be characterized by a predominantly humoral immune response (TH2) or a predominantly cellular immune response (TH1). This discovery was a crucial event in our understanding of how the host immune response is regulated, and has fundamental implications for vaccine design and disease pathogenesis. Dr. Mosmann is recognized by the Institute for Scientific Information as a highly cited scientist, and has won many honours and awards for his unique contributions to understanding of the immune system. Note that "highly cited" scientists comprise less than 0.5% of all publishing researchers in science.

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In vivo T cell functions are difficult to evaluate, because cytokine secretion phenotypes in addition to Th1, Th2 and Th0 may occur in vivo; and differentiation and selective growth of T cell subsets in vitro can rapidly obscure patterns that occur in vivo. We are using multicolor flow cytometry and Spot assays to detect the simultaneous expression of two or more cytokines by individual human or mouse T cells, to resolve the contributions of partial differentiation, stochastic variation and environmental effects to the spectrum of cytokines produced by individual cells. Short-term cloning experiments are being used to examine the relationship between T cell phenotypes in vivo, versus in long-term tissue culture. These methods are being applied to define the precise T cell phenotypes induced by vaccination and infection by different influenza strains in infants, adults and the elderly.

A Genechip analysis of T cell gene expression revealed that Amphiregulin, an EGF family member, is selectively expressed in activated mouse Th2 cells, and contributes to Th2-mediated elimination of a helminth parasite. This raises the possibility that Th2 cells could contribute to asthma both by enhancing the allergic response and by increasing tissue remodeling. Initial human experiments suggest that regulation of amhipregulin expression is more complex in humans, but still linked to a Type 2 response. A clinical study has been initiated to compare amphiregulin expression in asthmatic patients and controls.

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