Dendritic cells

Deficiency of Bim in dendritic cells contributes to over-activation of lymphocytes and autoimmunity. Chen, M. et al. Blood 16 January 2007 (doi:10.1182/blood-2006-11-056424)

The B-cell lymphoma 2 (BCL-2) family of proteins regulates the mitochondrial apoptotic pathway, and BCL-2 homology 3 (BH3)-only proteins, such as BIM (BCL-2-interacting mediator of cell death), regulate the initiation stage of apoptosis. BIM-deficient mice develop spontaneous systemic autoimmunity with significant expansion of T-cell numbers; the authors investigated the role of dendritic cells (DCs) in this process. Compared with wild-type DCs, DCs from BIM-deficient mice showed increased survival, were more efficient at stimulating T-cell activation both in vivo and in vitro and were able to induce the production of autoantibodies following adoptive transfer. Therefore, BIM-deficient DCs might contribute to the development of autoimmunity and overactivation of T cells in BIM-deficient mice.

Macrophages

Regulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-γ-mediated pathways. Liu, J. et al. J. Exp. Med. 16 January 2007 (doi:10.1084/jem.20061440)

Interleukin-27 (IL-27) is an IL-12-family member with both pro- and anti-inflammatory properties, and is composed of two subunits, Epstein–Barr virus-induced gene 3 (EBI3; also known as IL-27B) and p28. But how do inflammatory signals stimulate the production of IL-27? Liu et al. examined the transcriptional regulation of the p28 gene in mouse macrophages in response to lipopolysaccharide (LPS) and interferon-γ (IFNγ). LPS-induced p28 mRNA expression was dependent on the myeloid differentiation primary-response gene 88 (MyD88)-mediated pathway, and only partially dependent on the nuclear factor-κB (NF-κB)-family member c-REL. IFNγ-induced p28 mRNA expression, however, was partially dependent on the MyD88 pathway and independent of c-REL, but required the transcription factor IFN-regulatory factor 1 (IRF1). Additionally, the authors identified crucial promoter elements that mediate the c-REL-dependent and IRF1-dependent inductive effects of LPS and IFNγ, respectively, on p28 gene transcription.

T-cell responses

B and T lymphocyte attenuator regulates CD8+ T cell–intrinsic homeostasis and memory cell generation. Krieg, C. et al. Nature Immunol. 7 January 2007 (doi:10.1038/ni1418)

Accumulating data indicate that B- and T-lymphocyte attenuator (BTLA) is a negative regulator of T-cell activation, but its in vivo function is not clear. Consistent with its negative regulatory role, T cells from mice deficient in BTLA, or its ligand, were shown to be hyper-responsive. However, this was not due to loss of the co-inhibitory signal in the responding T cells but to increased numbers of CD8+ T cells with a memory phenotype, which are highly proliferative. Indeed, compared with wild-type T cells, BTLA-deficient T cells were more efficient generators of memory, although their response to antigen-specific priming was normal. Use of a competitive chimaera approach revealed that the loss of BTLA also results in enhanced homeostatic expansion. So, this study assigns two new roles for BTLA — regulation of T-cell memory formation and T-cell homeostasis.