Timothy Richard Mosmann, Ph.D.

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The Th1 and Th2 subsets of CD4+ T cells induce different types of effector functions that are useful in combating different pathogens. Th1 cells producing Interferon gamma induce cytotoxic, inflammatory responses that are most effective against intracellular parasites, whereas Th2 cells producing IL4 and IL5 induce successful responses against helminth parasites. Although naïve, uncommitted CD4 T cells can differentiate into Th1 or Th2 phenotypes within a few days of initial stimulation, they can also remain uncommitted. These primed, precursor cells (Thpp) produce IL-2 and proliferate rapidly, allowing expansion of antigen-specific cells during an immune response before commitment to a particular effector phenotype. Cells producing only IL-2 also persist for several weeks after immunization, suggesting that these cells may also provide an expanded pool of uncommitted T cells for subsequent immune responses. In common with Treg cells, Thpp express CD73, which can help to generate adenosine that contributes to immune suppression.

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.

Current Appointments

• Director - Center for Vaccine Biology and Immunology (SMD)
• Michael and Angela Pichichero Director in the David H. Smith Center for Vaccine Biology and Immunology - Center for Vaccine Biology and Immunology (SMD)
• Professor - Department of Microbiology and Immunology, Center for Vaccine Biology and Immunology (SMD)

Education
PhD Microbiology	University of British Columbia	1973
B. Sc. Microbiology	Rhodes University	1969
BS Chemistry, and Physiology	University of Natal	1968

Post-Doctoral Training & Residency
Glasgow University, Glasgow, Scotland; Immunology	1975 - 1977
Hospital for Sick Children, Toronto; Immunology	1973 - 1975

Recent Journal Articles
Showing the 5 most recent journal articles. (154 available)
Hilchey SP; Hyrien O; Mosmann TR; Livingstone AM; Friedberg JW; Young F; Fisher RI; Kelleher RJ; Bankert RB; Bernstein SH. "Rituximab immunotherapy results in the induction of a lymphoma idiotype-specific T-cell response in patients with follicular lymphoma: support for a "vaccinal effect" of rituximab." Blood. 2009; Epub 2009 Feb 04.
Mosmann TR; Kobie JJ; Lee FE; Quataert SA. "T helper cytokine patterns: defined subsets, random expression, and external modulation." Immunologic research. 2009; Epub 2009 Feb 06.
Lee HY; Hawkins E; Zand MS; Mosmann T; Wu H; Hodgkin PD; Perelson AS. "Interpreting CFSE Obtained Division Histories of B Cells in Vitro with Smith-Martin and Cyton Type Models." Bulletin of mathematical biology. 2009; Epub 2009 Apr 21.
Seavey MM; Mosmann TR. "Estradiol-induced vaginal mucus inhibits antigen penetration and CD8(+) T cell priming in response to intravaginal immunization." Vaccine. 2009; 27(17):2342-2349. Epub 2009 Feb 14.
Lee HY; Topham DJ; Park SY; Hollenbaugh J; Treanor J; Mosmann TR; Jin X; Ward B; Miao H; Holden-Wiltse J; Perelson AS; Zand M; Wu H. "Simulation and Prediction of the Adaptive Immune Response to Influenza A Virus Infection." Journal of virology. 2009; Epub 2009 May 13.