 Ph.D. (1973) |
Tim
Mosmann
Director, Vaccine Biology Initiative; Professor of Microbiology & Immunology Primary Academic Appointment: Center Affiliation: GEBS Cluster Affiliations: |
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| Contact Information: | ||
| University of Rochester School of Medicine and Dentistry 601 Elmwood Ave, Box 609 Rochester, New York 14642 |
Phone:
(585) 275-9120 E-Mail: tim_mosmann @urmc.rochester.edu |
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- Research Focus
- Immune regulation by T cell subsets and their cytokines
- Research Overview
- 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 six 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.
- Recent Publications
- Zaiss DM, Sijts AJ, Mosmann TR Enumeration of cytotoxic CD8 T cells ex vivo during the response to Listeria monocytogenes infection. Infect Immun. 2008 Aug 4;
- Rebhahn JA, Bishop C, Divekar AA, Jiminez-Garcia K, Kobie JJ, Lee FE, Maupin GM, Snyder-Cappione JE, Zaiss DM, Mosmann TR Automated analysis of two- and three-color fluorescent Elispot (Fluorospot) assays for cytokine secretion. Comput Methods Programs Biomed. 2008 Jul 19;
- Seavey MM, Mosmann TR"Immunoregulation of fetal and anti-paternal immune responses." Immunol Res. 2008;40(2):97-113
- Richter M, Ray SJ, Chapman TJ, Austin SJ, Rebhahn J, Mosmann TR, Gardner H, Kotelianski V, Defougerolles AR, Topham DJ. "Collagen Distribution and Expression of Collagen-Binding {alpha}1beta1 (VLA-1) and {alpha}2beta1 (VLA-2) Integrins on CD4 and CD8 T Cells during Influenza Infection." J Immunol. 2007 Apr 1;178(7):4506-16.
- Authors: Zaiss DM, Yang L, Shah PR, Kobie JJ, Urban JF, Mosmann TR "Amphiregulin, a TH2 Cytokine Enhancing Resistance to Nematodes." Science. 2006 Dec 15;314(5806):1746
- Seavey MM, Mosmann TR "Paternal Antigen-Bearing Cells Transferred during Insemination Do Not Stimulate Anti-Paternal CD8+ T Cells: Role of Estradiol in Locally Inhibiting CD8+ T Cell Responses." J Immunol. 2006 Dec 1;177(11):7567-78
- Kobie JJ, Shah PR, Yang L, Rebhahn JA, Fowell DJ, Mosmann TR. "T regulatory and primed uncommitted CD4 T cells express CD73, which suppresses effector CD4 T cells by converting 5'-adenosine monophosphate to adenosine." J Immunol. 2006 Nov 15;177(10):6780-6
- Ma J, Mosmann T, Wu H "Design considerations for a web-based database system of ELISpot assay in immunological research." AMIA Annu Symp Proc. 2005;:1039
- Snyder-Cappione JE, Divekar AA, Maupin GM, Jin X, Demeter LM, Mosmann TR. "HIV-specific cytotoxic cell frequencies measured directly ex vivo by the Lysispot assay can be higher or lower than the frequencies of IFN-gamma-secreting cells: anti-HIV cytotoxicity is not generally impaired relative to other chronic virus responses." J Immunol. 2006 Feb 15;176(4):2662-8.
- Divekar AA, Zaiss DM, Lee FE, Liu D, Topham DJ, Sijts AJ, Mosmann TR. "Protein vaccines induce uncommitted IL-2-secreting human and mouse CD4 T cells, whereas infections induce more IFN-gamma-secreting cells." J Immunol. 2006 Feb 1;176(3):1465-73.
- Yang L, Kobie JJ, Mosmann TR. "CD73 and Ly-6A/E distinguish in vivo primed but uncommitted mouse CD4 T cells from type 1 or type 2 effector cells." J Immunol. 2005 Nov 15;175(10):6458-64.
- Lee F. E, Walsh E. E, Falsey A. R, Liu N, Liu D, Divekar A, Snyder-Cappione J. E, Mosmann, T. R. "The balance between influenza- and RSV-specific CD4 T cells secreting IL-10 or IFNgamma in young and healthy-elderly subjects." Mech Ageing Dev 2005.
- Mosmann, T. R., H. Cherwinski, et al. "Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. 1986." J Immunol 175(1): 5-14, 2005.
- Mosmann TR, Livingstone AM. Dendritic cells: the immune information management experts. Nat Immunol. 5:564-566, 2004.
- Mosmann TR, Snyder JE. How to spot a real killer. Trends Immunol 24:231, 2003
- Snyder JE, Bowers WJ, Livingstone AM, Lee FE, Federoff HJ, Mosmann TR. Measuring the frequency of mouse and human cytotoxic T cells by the Lysispot assay: independent regulation of cytokine secretion and short-term killing. Nat Med. 9:231-6, 2003.
- Wang X, Mosmann TR. In vivo priming of CD4 T Cells that produce interleukin (IL)-2 but not IL-4 or interferon (IFN)-gamma, and can subsequently differentiate into IL-4 or IFN-gamma secreting cells. J. Exp. Med. 194:1069-1080, 2001.
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