Primary Academic Appointment:
  Dept. of Microbiology and Immunology

Center Affiliation:
  Center for Vaccine Biology and Immunology

GEBS Cluster Affiliations:
 Immunology, Microbiology, and Virology - IMV

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

Immune regulation by T cell subsets and their cytokines

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. We are currently analyzing the functions and differentiation potential of these cells.

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 have developed two new assays - a multicolor Elispot assay to detect the simultaneous expression of two or more cytokines by individual human or mouse T cells; and a cytotoxicity assay that can detect individual cytotoxic cells. These assays are being used directly ex vivo to define the T cell phenotypes induced during successful and unsuccessful immune responses to human papillomavirus or HIV infections.

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.

Akai PS, Mosmann TR. Primed and replicating but uncommitted T helper precursor cells show kinetics of differentiation and commitment similar to those of naive T helper cells. Microbes Infect. 1:51-8, 1999.

Li L, Xia Y, Nguyen A, Lai YH, Feng L, Mosmann TR, Lo D. Effects of Th2 cytokines on chemokine expression in the lung: IL-13 potently induces eotaxin expression by airway epithelial cells. J. Immunol 162:2477-87, 1999.

Lai YH, Mosmann TR. Mouse IL-13 enhances antibody production in vivo and acts directly on B cells in vitro to increase survival and hence antibody production. J Immunol 162:78-87, 1999.