CD8+ T cells as a source of IFN-γ production in human cutaneous leishmaniasis

Background: in 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 findings: cd4+/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 foldexpression 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/significance: collectively,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 antigenspecific ifn-γ producing cd4+ th1 cells,but also through ifn-γ producing cd8+ t cells. © 2010 nateghi rostami et al.