Abstract
BackgroundIn human leishmaniasis Th1/Th2 dichotomy similar to murine model is not clearly defined and surrogate marker(s) of protection is not yet known. In this study, Th1/Th2 cytokines (IL-5, IL-10, IL-13 and IFN-γ) profile induced by purified CD4+/CD8+ T cells in response to Leishmania antigens were assessed at transcript and protein levels in 14 volunteers with a history of self-healing cutaneous leishmaniasis (HCL) and compared with 18 healthy control volunteers.Methodology/Principal FindingsCD4+/CD8+/CD14+ cells were purified from peripheral blood using magnetic beads; CD4+/CD8+ T cells were co-cultured with autologous CD14+ monocytes in the presence of soluble Leishmania antigens (SLA). Stimulation of either CD4+ T cells or CD8+ T cells of HCL volunteers with SLA induced a significantly (P<0.05) higher IFN-γ production compared with the cells of controls. Upregulation of IFN-γ gene expression in CD4+ cells (P<0.001) and CD8+ cells (P = 0.006) of HCL volunteers was significantly more than that of controls. Significantly (P<0.05) higher fold-expression of IFN-γ gene was seen in CD4+ cells than in CD8+ cells. In HCL volunteers a significantly (P = 0.014) higher number of CD4+ cells were positive for intracellular IFN-γ production than CD8+ cells.Conclusions/SignificanceCollectively, the volunteers have shown maintenance of specific long-term immune responses characterized by a strong reaction to leishmanin skin test and IFN-γ production. The dominant IFN-γ response was the result of expansion of both CD4+ and CD8+ T cells. The results suggested that immune response in protected individuals with a history of zoonotic cutaneous leishmaniasis (ZCL) due to L. major is mediated not only through the expansion of antigen-specific IFN-γ producing CD4+ Th1 cells, but also through IFN-γ producing CD8+ T cells.
Highlights
Leishmaniasis is expanding both by increasing the incidence rate in endemic foci and extending the disease to new regions [1,2]
The results suggested that immune response in protected individuals with a history of zoonotic cutaneous leishmaniasis (ZCL) due to L. major is mediated through the expansion of antigenspecific IFN-c producing CD4+ Th1 cells, and through IFN-c producing CD8+ T cells
CD4+ T cells upon activation differentiate into functional effector Th1 and/or Th2 subsets and the outcome of Leishmania major infection in murine model is dependent upon the type of immune response generated: in most strains of mice L. major infection induces a Th1 type of response associated with a high level of IFN-c, low level of IL-4, and similar to human cutaneous leishmaniasis the lesion(s) heals spontaneously and the animals are protected against further infection; whereas L. major infection in BALB/c mice induces a Th2 response and a high level of IL-4 and low level of IFN-c, as a result the disease is fetal
Summary
Leishmaniasis is expanding both by increasing the incidence rate in endemic foci and extending the disease to new regions [1,2]. CD4+ T cells upon activation differentiate into functional effector Th1 and/or Th2 subsets and the outcome of Leishmania major infection in murine model is dependent upon the type of immune response generated: in most strains of mice L. major infection induces a Th1 type of response associated with a high level of IFN-c, low level of IL-4, and similar to human cutaneous leishmaniasis the lesion(s) heals spontaneously and the animals are protected against further infection; whereas L. major infection in BALB/c mice induces a Th2 response and a high level of IL-4 and low level of IFN-c, as a result the disease is fetal [8,9]. Th1/Th2 cytokines (IL-5, IL-10, IL-13 and IFN-c) profile induced by purified CD4+/CD8+ T cells in response to Leishmania antigens were assessed at transcript and protein levels in 14 volunteers with a history of self-healing cutaneous leishmaniasis (HCL) and compared with 18 healthy control volunteers
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