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CHARACTERIZATION OF THE EARLY CELLULAR IMMUNE RESPONSE TO LEISHMANIA MAJOR USING PERIPHERAL BLOOD MONONUCLEAR CELLS FROM LEISHMANIA-NAIVE HUMANS

While the response to Leishmania major is well characterized in mice, there is much less known about the human immune response, particularly early after exposure to the parasite. Therefore, we developed a primary in vitro (PIV) system that allowed us to address these questions. We co-cultured peripheral blood mononuclear cells from Leishmania-naive donors with L. major parasites and found that the responding PIV cells produced interferon- and interleukin-12 (IL-12). When restimulated, these PIV cells also occasionally produced IL-5. Both CD4 and CD8 cells and both HLA class I and II cell activation pathways appeared to play a role in the PIV system, and cell activation was dependent upon the presence of antigen-presenting cells. Moreover, PIV cells generated with L. major showed considerable cross-reactivity with other species of Leishmania. Finally, the PIV cells augmented intracellular killing of L. major when they were co-cultured with macrophages infected with the parasite.

Received March 22, 2004. Accepted for publication June 11, 2004.

Acknowledgments: We thank Drs. Gregory DeKrey, Lamine Mbow, Claudia Brodskyn, and Dean Gillespie for their insightful discussions and assistance. We are also indebted to Monica Estay, Julie Bleyenberg, Jeremy Jones, and Leanna Nosbisch for their excellent technical assistance.

Financial support: This work was supported by National Institutes of Health grants AI-27511 and AI-29955, the Colorado Institute for Research in Biotechnology, and the International Foundation for Ethical Research.

Authors’ addresses: Kathleen A. Rogers, Division of Geographic Medicine and Infectious Diseases, Tufts-New England Medical Center, Boston, MA 02111, Telephone: 617-636-8437, Fax: 617-636-5292, E-mail: KRogers{at}tufts-nemc.org. Richard G. Titus, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1619, Telephone: 970-491-4964, Fax: 970-491-0603, E-mail: rtitus{at}colostate.edu.

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