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

The clinical manifestation of leptospirosis is highly variable: from asymptomatic to severe, and potentially fatal. The outcome of the disease is usually determined in the immunological phase, beginning in the second week of symptoms. The underlying mechanisms, predictive factors, and individual immune response that contribute to clinical variations are not well understood. The aim of this study was to determine the specific CD4+ T-cell reactivity and cytokine release after stimulation with leptospiral antigens in patients with leptospirosis of different disease severity (patients with mild and severe symptoms) and in control subjects (with and without proven exposure to Leptospira ). Whole blood specimens were stimulated with Leptospira antigens in-vitro . Subsequently, intracellular staining of cytokines was performed, and flow cytometry was used to assess the expression of CD40-ligand (CD40L) and the production of interferon (IFN)γ, interleukin (IL)-10, IL-2, and tumor necrosis factor (TNF)α by CD4+ T-cells. The production of inflammatory cytokines such as TNFα by CD4 + T-cells after stimulation with leptospiral antigens was highest in patients with severe disease. In contrast, the ratio of IL-10/TNFα production was highest in exposed subjects compared to patients with mild and severe disease. Pro-inflammatory cytokines such as TNFα may be a useful marker of the severity of the immunological phase of leptospirosis. IL-10 production by T-cells after antigen-specific stimulation may indicate a more successful down-regulation of the inflammatory response and may contribute to an asymptomatic course of the disease.