In Brief

Insect immunity

Downreguation of the Drosophila immune response by peptidoglycan-recognition proteins SC1 and SC2. Bischoff, V. et al. PLoS pathog. 2, e14 (2006)

The function of peptidoglycan-recognition proteins (PGRPs) that have amidase activity, such as PGRP-SC1 and PGRP-SC2, in Drosophila spp. is not clear. To examine the role of these proteins in vivo, PGRP-SC-deficient flies were generated using RNA interference. One of the two distinct signalling pathways involved in antimicrobial host defence in Drosophila spp., the IMD (Immune deficiency) signalling pathway, is over-activated in these mutant flies following bacterial challenge. Activation of the IMD pathway is also increased in larvae with reduced levels of PGRP-SC1 and PGRP-SC2 after feeding on Escherichia coli, compared to wild-type larvae. These mutant larvae are highly susceptible to infection and have higher mortality rates, caused by over-activation of the IMD pathway. Therefore, this study indicates that PGRPs with amidase activity have an essential role in dampening the IMD pathway, thereby controlling the intensity of the response to bacteria in Drosophila spp. and preventing bacteria-induced larval death.

Regulatory T cells

Toll-like receptor 2 controls expansion and function of regulatory T cells. Sutmuller, R. P. M. et al. J. Clin. Invest. 116, 485–494 (2006)

The mechanism by which intrinsic CD4⁺CD25⁺ regulatory T (T_Reg) cells are controlled is not fully understood. Recent studies have shown that Toll-like receptors (TLRs) are expressed by T_Reg cells. This study shows that engagement of TLR2, but not TLR4 or TLR9, on T_Reg cells resulted in the proliferation of these cells both in vitro and in vivo. This proliferation was accompanied by a temporal abrogation of the suppressive function of the T_Reg cell. Transfer of TLR2-sufficient T_Reg cells into TLR2-deficient mice inhibited the immune response to Candida albicans, whereas co-administration of a TLR2 ligand resulted in the loss of the suppressive effect of the T_Reg cells and reduced fungal outgrowth. Therefore, the temporal abrogation of T_Reg-cell-associated suppression by TLR2 signalling allowed for an increased antifungal response, indicating an important link between TLRs and T_Reg cells in the control of an immune response.

Immunotherapy

Interleukin-15 rescues tolerant CD8⁺ T cells for use in adoptive immunotherapy of established tumors. Teague, R. M. et al. Nature Med. 12, 335–341 (2006)

The eradication of tumours by CD8⁺ T cells is often impeded by the fact that T cells are tolerant to most tumour antigens. To find ways to overcome this tolerance, the authors used a mouse model, in which T-cell-receptor-transgenic T cells are tolerant to a candidate tumour antigen transgene that is expressed in the liver. In response to antigen, the transgenic T cells failed to proliferate or form stable immune synapses in vitro, although they showed cytolytic activity when stimulated in vivo. Further studies showed that treatment of the tolerant T cells with interleukin-15 (IL-15) could rescue all effector functions in vivo, including proliferation. Importantly, transfer of IL-15-treated tolerant T cells to mice bearing established tumours caused complete tumour eradication in 50% of the mice, indicating that IL-15 could be used to enhance tumour immunotherapy.