Leptospira interrogansActivation of Human Peripheral Blood Mononuclear Cells: Preferential Expansion of TCRγδ+ T Cells vs TCRαβ+ T Cells

Abstract

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-γ, IL-12, and TNF-α. 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 γ/δ T cells. These cultures showed a 10- to 50-fold expansion of γ/δ 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 γδ T cell or NK cell expansion, but induced significant αβ T cell expansion. Vγ9/Vδ2 were expressed on all γ/δ T cells expanded by exposure of PBMC to Leptospira. Leptospira stimulation of purified TCRγδ+ T cells, obtained from 8-day cultures of Leptorspira-stimulated PBMC, induced high levels of IFN-γ production, but no cell proliferation, suggesting that such stimulation of γδ 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 TCRγδ+ T cells. These results indicate that Leptospira can activate γδ T cells and αβ T cells and will guide further investigations into the roles of these T cell populations in host defense and/or the pathology of leptospirosis.

Atypical lymphocytosis in leptospirosis: a cohort of hospitalized cases between 1996 and 2009 in State of Rio de Janeiro, Brazil

“…Atypical lymphocytes have been best studied from the blood of patients with Epstein-Barr virus (EBV), cytomegalovirus (CMV), toxoplasma infections, Q fever, rubella, roseola, herpes simplex, hemorrhagic fever, Rickettisialpox, mumps, adenovirus, influenza, tuberculosis, varicella, syphilis, HIV (types 1 and 2), hepatitis A, hepatitis B, Mycoplasma pneumoniae and Listeria monocytogenes 20 . There is only one case report associating atypical lymphocytes and γδ T cell expansion with leptospirosis 12 , and the main role of γδ T cells in the immune response to leptospirosis remains unclear 21 . γδ T cells constitute a small proportion (1-5%) of the blood and peripheral organ circulating lymphocytes.…”

Specific CD4+T-Cell Reactivity and Cytokine Release in Different Clinical Presentations of Leptospirosis

“…Comparisons to previous research are difficult, since only reports about cytokine concentrations in serum specimens have been published; no data have been published about human CD4 ϩ T-cell cytokine release upon Leptospira-specific short-term stimulation in relation to the clinical severity of leptospirosis. One previous study did demonstrate, though, that naive human peripheral blood mononuclear cells (PBMC) in long-term culture can be stimulated by leptospiral antigens to produce IFN-␥, IL-12, and TNF-␣ (23,24).…”

Protection againstLeptospira interrogansSensu Lato Challenge by DNA Immunization with the Gene Encoding Hemolysin-Associated Protein 1

“…Recent data showed that Th1 responses play an important role in the protective effect against disease. L. interrogans could activate ␥␦ and ␣␤ T-cell populations (31), and the roles of these populations in host defense and the pathology of leptospirosis have been investigated. Leptospire infection has been shown to induce a type 1 response comprising CD4 and ␥␦ T lymphocytes; however, although this response was too weak to prevent the establishment of chronic infection (46), a vaccine composed of dead Leptospira together with an aluminum hydroxide adjuvant induced a potent Th1-type cellular response in cattle which was associated with protective immunity to serovar hardjo infection (45,13).…”