In Brief

Antigen presentation

The dominant role of CD8⁺ dendritic cells in cross-presentation is not dictated by antigen capture. Schnorrer, P. et al. Proc. Natl Acad. Sci. USA 103, 10729–10734 (2006)

Mouse splenic CD8⁺ dendritic cells (DCs) are unique in their ability to present exogenous antigen by MHC class I molecules, a process known as cross-presentation. However, it was not known, until now, if this ability is due to a difference in antigen-capturing ability or if this cell population has specialized machinery for this process. Schnorrer et al. examined the uptake and presentation of different forms of a model antigen by the three main splenic DC subsets and found that all subsets captured comparable amounts of antigen and presented it on their MHC class II molecules. Therefore, the ability of CD8⁺DCs to cross-present antigen cannot be attributed to a difference in their ability to capture antigen, indicating that this cell type must have specialized machinery for cross-presentation.

Regulatory T cells

Heat shock protein 60 enhances CD4⁺CD25⁺ regulatory T cell function via innate TLR2 signalling. Zanin-Zhorov, A. et al. J. Clin. Invest. 116, 2022–2032 (2006)

How are the regulators regulated? This paper shows that heat-shock protein 60 (HSP60) can increase the suppressive activity of human CD4⁺CD25⁺ regulatory T (T_Reg) cells. Treatment of purified T_Reg cells with HSP60 before stimulation with CD3-specific antibody enhanced their ability to suppress both pro-inflammatory cytokine secretion by and proliferation of CD4⁺CD25⁻ effector T cells in co-culture. The HSP60-derived peptide p227 had a similar effect. The effects of HSP60 or p227 on the T_Reg cells were mediated through Toll-like receptor 2 (TLR2), as TLR2-specific blocking antibody abrogated the effects. The mechanism of suppression by HSP60-treated T_Reg cells required both cell–cell contact, through interactions with cytotoxic T-lymphocyte antigen 4, and the inhibitory cytokines transforming growth factor-β and interleukin-10. So, signals from an innate receptor delivered by a self-protein might regulate adaptive immune responses.

Immune responses

Interleukin 12p40 is required for dendritic cell migration and T cell priming after Mycobacterium tuberculosis infection. Khader, S. A. et al. J. Exp. Med. 203, 1805–1815 (2006)

Adaptive T-cell immunity to respiratory infections depends on the migration of dendritic cells (DCs) from the lung to the draining lymph nodes and their subsequent activation of T cells. For effector T-cell development, these DCs must produce interleukin-12 (IL-12)p70, which is made up of IL-12p35 and IL-12p40. Khader et al. investigated whether there might be an independent role for IL-12p40 in lung-DC migration and CD4⁺ T-cell activation following Mycobacterium tuberculosis infection, given that there is early secretion of IL-12p40 during lung inflammation. They found that the migration of IL-12p40-deficient DCs from the lungs of M. tuberculosis-exposed mice was defective and that these cells were not able to activate naive CD4⁺ T cells in vivo; treatment of the DCs with IL-12p40 homodimer, however, restored these properties. Khader et al. have defined a novel and important role for IL-12p40 in the initiation of the lung's adaptive immune response to pathogen challenge.