In earlier work, this group showed that, after infection of mice with the parasite Leishmania major, TReg cells accumulate in the skin and draining lymph nodes, where they impede effector-T-cell-mediated clearance of the pathogen. To assess the specificity of these TReg cells, the authors tested the ability of the cells to proliferate in vitro in response to L. major-infected bone-marrow-derived dendritic cells (BMDCs). Surprisingly, most of the CD4+CD25hi T cells isolated from the skin-draining lymph nodes of chronically infected mice proliferated under these conditions. These CD4+CD25hi T cells were indeed TReg cells (and not activated CD4+ effector T cells, which also express CD25) because they were shown to express the TReg-cell-specific marker forkhead box P3 (FOXP3) and, in response to L. major-infected BMDCs, they secreted the regulatory cytokine interleukin-10 (IL-10) and only small amounts of the effector-T-cell cytokine interferon-γ. Moreover, the CD4+CD25hi T-cell population suppressed in vitro proliferation and cytokine release by activated CD4+CD25− T cells in an antigen-dependent manner.
Next, the authors carried out experiments to rule out the possibility that the proliferation of TReg cells from the infected mice was caused by exposure to microbial products or nonspecific activation. They showed that TReg-cell proliferation was abolished when the cells were exposed to BMDCs that lacked MHC class II molecules or to BMDCs that were activated with lipopolysaccharide and CD40-specific antibody, confirming that the TReg-cell response was antigen dependent.
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