CD8+ T Cells as a Source of IFN-γ Production in Human Cutaneous Leishmaniasis

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.

Glycyrrhizic Acid-Mediated Subdual of Myeloid-Derived Suppressor Cells Induces Antileishmanial Immune Responses in a Susceptible Host

“…Immunotherapy against visceral leishmaniasis is challenging partly because of immunosuppression (31)(32)(33)(34). Myeloid cells are a major source of T cell suppression in many diseases, including leishmaniasis (13).…”

Protective and Pathological Functions of CD8+T Cells in Leishmania braziliensis Infection

“…ϩ T cells (34). Recently, in BALB/c mice vaccinated with Toll-like receptor (TLR) ligands (DNA priming) plus TLR1 and TLR2 agonists as an adjuvant, protection against Leishmania (Viannia) panamensis was found to be dependent on the memory of CD8 ϩ T cells and on IFN-␥ production (35).…”

Isolation of Aureobasidium pullulans and the effect of different conditions for pullulanase and pullulan production

“…This is also the case in visceral leishmaniasis caused by L. donovani , in mice and humans where IFN-γ-producing Th1 cells protect against severe disease (Kushawaha, Gupta, Sundar, Sahasrabuddhe, & Dube, 2011). In human cutaneous leishmaniasis IFN-γ production by CD8+ T cells seems to contribute to disease resolution (Mary, Auriault, Faugère, & Dessein, 1999; Nateghi Rostami et al, 2010). However, as demonstrated by Leishmania infection models using CD4 or CD8 deficient mice, while CD4 T cells are required for resolution of disease (Chakkalath et al, 1995), the role of CD8 T cells in immunity to cutaneous or visceral leishmaniasis seems to depend on the model used (Belkaid, Von Stebut, et al, 2002; Erb, Blank, Ritter, Bluethmann, & Moll, 1996; Gomes-Pereira, Rodrigues, Rolão, Almeida, & Santos-Gomes, 2004; Huber, Timms, Mak, Röllinghoff, & Lohoff, 1998; Tsagozis, Karagouni, & Dotsika, 2005).…”