Immunology Graduate Group

Jay P. Farrell, Ph.D.
Department of Parasitology,
School of Veterinary Medicine

Office Phone: (215) 898-8561
Email:  farrellj@phl.vet.upenn.edu

Education:
B.S., Biology, Lafayette College
Ph.D., Zoology, Rutgers University
Post Doctoral Fellow, Rutgers University

Research Interests

Immunological aspects of cutaneous and visceral leishmaniasis

Research Summary

Our research centers on the identification of factors which regulate the activation and function of T cell subsets during murine infections with the protozoan parasite, Leishmania major. L. major produces either of two divergent patterns of infection in inbred strains of mice. Most strains of mice develop infections which spontaneously resolve, while other strains, including BALB/c mice, develop progressive, 
non-healing infections which are ultimately fatal. Resistance and susceptibility is determined by the activation of different subsets of T helper cells. Thus, resistance is associated with the activation of Th1 cells which produce IL-2 and IFN-g, while susceptibility correlates with the activation of Th2 cells which produce IL-4, IL-5, and IL-10. These divergent patterns of Th subset activation, which can be altered experimentally by in vivo cytokine and anti-cytokine therapy, as well as immunization, have made the L. major-infected mouse a popular infectious disease model for the in vivo study of T cell regulation.

Our particular interest is the mechanism by which the balance between Th1 and Th2 cells is regulated during chronic stages of infection and how specific cytokine immunotherapy may promote the predominance of one subset over the other. We have previously shown that in vivo treatment with anti-IL-4 antibody, IL-12 or IFN-g, in combination with the anti-leishmanial drug, sodium stibogluconate, can induce cure and a Th2 to Th1 switch in BLAB/c mice with chronic non-healing L. major infections. More recently, we have identified PGE2 and TGFb as factors which may influence both in vivo cytokine production and the development of resistance. Our goal is to understand the basic mechanisms by which these and other factors regulate T cell responses.

Course of a Leishmania major infection in susceptible BALB/c mice. Mice were treated at 2 weeks of infection with IL-12 and indomethacin, a cyclooxygenase inhibitor which blocks the production of prostaglandins. Treatment with a com- bination of IL-12 and indomethacin induced healing of the infection and the development of a TH1 type immune response (high IFN-y production, low IL-4 production). Treatment with either IL-12 or indomethacin alone did not induce healing or a TH1 response (not shown). These results suggest that prostaglan- dins may affect the in vivo response to IL-12 immunotherapy.

 

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