T Cell-Derived IL-10 Determines Leishmaniasis Disease Outcome and Is Suppressed by a Dendritic Cell Based Vaccine

In the murine model of leishmania major infection,resistance or susceptibility to the parasite has been associated with the development of a th1 or th2 type of immune response. recently,however,the immunosuppressive effects of il-10 have been ascribed a crucial role in the development of the different clinical correlates of leishmania infection in humans. since t cells and professional apc are important cellular sources of il-10,we compared leishmaniasis disease progression in t cell-specific,macrophage/neutrophil-specific and complete il-10-deficient c57bl/6 as well as t cell-specific and complete il-10-deficient balb/c mice. as early as two weeks after infection of these mice with l. major,t cell-specific and complete il-10-deficient animals showed significantly increased lesion development accompanied by a markedly elevated secretion of ifn-γ or ifn-γ and il-4 in the lymph nodes draining the lesions of the c57bl/6 or balb/c mutants,respectively. in contrast,macrophage/neutrophil-specific il-10-deficient c57bl/6 mice did not show any altered phenotype. during the further course of disease,the t cell-specific as well as the complete il-10-deficient balb/c mice were able to control the infection. furthermore,a dendritic cell-based vaccination against leishmaniasis efficiently suppresses the early secretion of il-10,thus contributing to the control of parasite spread. taken together,il-10 secretion by t cells has an influence on immune activation early after infection and is sufficient to render balb/c mice susceptible to an uncontrolled leishmania major infection. © 2013 schwarz et al.