3c), suggesting that lymphoid cells are involved in the increase in this population during infection with P. yoelii. Because lymphoid cells were required for the accumulation of MHC II+CD11c−CD3−CD19−IgM− cells during infection with P. yoelii, the following two possibilities

Selleckchem Ibrutinib were considered: (1) these cells were derived from the lymphoid lineage; or (2) they were of myeloid lineage and became MHC II+CD11c−IgM− cells under the influence of lymphocytes during infection. To examine these possibilities, Rag-2−/− mice (CD45.2+) were adoptively infused with splenocytes, which contain lymphoid cells, from B6.Ly5.1 (CD45.1+) mice. These mice were maintained for 3 weeks to allow homeostatic proliferation of the donor cells and were then infected with P. yoelii [24]. Eight days post-infection, accumulation of MHC II+CD11c−CD3−CD19−IgM− cells was

separately examined in CD45.1+ and CD45.1− populations (Fig. 4). The number of MHC II+CD11c−CD3−CD19−IgM− cells did not significantly increase in the donor CD45.1+ population; however, the number in the host CD45.2+ population did significantly increase, suggesting that the majority of MHC II+CD11c−CD3−CD19−IgM− cells that are derived from the myeloid lineage accumulate in the spleens of P. yoelii-infected mice mainly have a non-lymphoid lineage. Thus, it was concluded that MHC II+CD11c−CD3−CD19−IgM− cells that are derived from the myeloid SCH772984 mw lineage accumulate in the spleens of P. yoelii-infected mice under the influence FER of lymphocytes. The functional capacities of MHC-II+CD11c− non-lymphoid cells that accumulate in the spleen as a defense mechanism against P. yoelii infection were examined. First, purified populations of MHC II+CD11c−CD3−CD19−IgM− cells

were incubated with iRBCs and production of TNF-α, IL-6 and IL-12 evaluated (Fig. 5). Conventional DCs from uninfected mice were used as positive controls. In response to iRBC, MHC II+CD11c−CD3−CD19−IgM− cells from infected mice produced TNF-α and IL-6, but not IL-12. Production of IL-10 was undetectable (data not shown). Second, the ability of these cells to present antigens to CD4+ T cells was evaluated by using OT-II OVA-specific TCR transgenic mice (Fig. 6). OT-II mice were immunized with OVA to enrich memory/effector type OT-II cells that are sensitive to the antigen presentation of OVA. MHC II+ subpopulations isolated from the spleens of infected and uninfected mice were pulsed with OVA323–339 or OVA and cocultured with OT-II cells. OT-II cell proliferation was assessed on the basis of diminution in CFSE and the amount of IL-2 production, which was determined by ELISA. MHC II+CD11chi DCs from both uninfected and infected mice efficiently stimulated proliferation of, and IL-2 production by, OT-II cells.