In Brief

Dendritic cells

Cutting edge: B220⁺CCR9⁻ dendritic cells are not plasmacytoid dendritic cells but are precursors of conventional dendritic cells Segura, E. et al. J. Immunol. 1 Jul 2009 (doi:10.4049/jimmunol.0901524)

A study published by Eugene Butcher and colleagues in Nature Immunology last year suggested that differential expression of CC-chemokine receptor 9 (CCR9) could distinguish functional subsets of plasmacytoid dendritic cells (pDCs). However, in this study, José Villadangos and colleagues show that CD11c⁺B220⁺ cells that lack CCR9 expression cannot be classified as pDCs. The CCR9⁻ cells did not express some classical pDC markers but they did express markers of conventional DCs, and did not produce interferon-α after stimulation. The B220⁺CCR9⁻ cells were also functionally comparable to conventional DCs in terms of their ability to present exogenous antigens on MHC class I and II molecules. B220⁺CCR9⁻ cells differentiated into the two main populations of conventional splenic DCs after adoptive transfer in vivo. These results indicate that B220⁺CCR9⁻ cells are not pDCs but precursors of conventional DCs.

T cell differentiation

Human dendritic cells induce the differentiation of interleukin-21-producing T follicular helper-like cells through interleukin-12 Schmitt, N. et al. Immunity 11 Jul 2009 (doi:10.1016/j.immuni.2009.04.016)

This paper extends our knowledge of the developmental pathway of human T follicular helper (T_FH) cells, which provide help for antibody-producing B cells in germinal centres by producing interleukin-21 (IL-21). The authors showed that IL-12 produced by activated dendritic cells (DCs) can induce naive CD4⁺ T cells to secrete IL-21 in vitro. IL-12 is a potent inducer of T_H1 cells, and indeed most of the IL-21-producing cells also produced interferon-γ (IFNγ); however, there was also a small population of IFNγ⁻IL-21⁺ cells that lacked T-bet expression. Human CD4⁺ T cells primed in the presence of IL-12 could induce naive B cells to produce immunoglobulins. IL-12 could also induce memory CD4⁺ T cells to produce IL-21. This role for IL-12 in the induction of IL-21-producing T_FH cells is not shared by mice, in which IL-6 and IL-21 have been shown to be important for T_FH cell development.

Tumour immunology

Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies Peggs, K. S. et al. J. Exp. Med. 6 Jul 2009 (doi:10.1084/jem.20082492)

Antibodies that block cytotoxic T lymphocyte antigen 4 (CTLA4) have been used to increase antitumour immune responses, but it is unclear whether effector T cells or regulatory T (T_Reg) cells are the target of this inhibition. The authors carried out suppression assays using combinations of effector and T_Reg cells from wild-type or transgenic mice that expressed human CTLA4. Blocking CTLA4 on wild-type effector T cells with an antibody that targets mouse CTLA4 resulted in increased baseline effector T cell proliferation, but blocking CTLA4 on T_Reg cells had a more modest effect; blocking both T cell subsets indicated a potential additive effect. Blocking CTLA4 on both effector and T_Reg cells in vivo also had the highest antitumour activity and mouse survival rates, indicating that targeting both T cell subsets would have the greatest benefit during cancer immunotherapy.