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Leptospira interrogans Activation of Human Peripheral Blood Mononuclear Cells: Preferential Expansion of TCR⁺ T Cells vs TCR⁺ T Cells ¹

Gary R. Klimpel^2,*, Michael A. Matthias and Joseph M. Vinetz^*,

Departments of ^* Microbiology and Immunology and Pathology, World Health Organization Collaborating Center for Tropical Diseases, University of Texas Medical Branch, Galveston, TX 77555

Innate and adaptive immune responses induced by leptospirosis have not been well characterized. In this study we show that in vitro exposure of naive human PBMC to Leptospira interrogans results in cell proliferation and the production of IFN-, IL-12, and TNF-. Cell proliferation was highest when using high numbers of Leptospira. Optimal cell proliferation occurred at 6–8 days, and the majority of cells contained in these cultures were / T cells. These cultures showed a 10- to 50-fold expansion of / T cells compared with the initial cellular input. Additionally, these cultures contained elevated numbers of NK cells. In contrast, exposure of PBMC to low numbers of Leptospira failed to induce T cell or NK cell expansion, but induced significant T cell expansion. V9/V2 were expressed on all / T cells expanded by exposure of PBMC to Leptospira. Leptospira stimulation of purified TCR⁺ T cells, obtained from 8-day cultures of Leptorspira-stimulated PBMC, induced high levels of IFN- production, but no cell proliferation, suggesting that such stimulation of T cells did not depend on specialized accessory cells or Ag processing. Finally, in patients with acute leptospirosis, there was a significant (4- to 5-fold) increase in the number of peripheral blood TCR⁺ T cells. These results indicate that Leptospira can activate T cells and T cells and will guide further investigations into the roles of these T cell populations in host defense and/or the pathology of leptospirosis.

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