In this issue
In this issue
Article first published online: 28 NOV 2011
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
European Journal of Immunology
Volume 41, Issue 12, pages 3388–3389, December 2011
How to Cite
(2011), In this issue. Eur. J. Immunol., 41: 3388–3389. doi: 10.1002/eji.201190071
- Issue published online: 28 NOV 2011
- Article first published online: 28 NOV 2011
- Cited By
The cover image shows immunohistological analysis of a spleen section from QMxB6 mice 96 hours after immunization with NP-Ficoll. IgD staining (brown) determines the B-cell follicles and NP-staining (blue) the antibody-producing cells; plasmablasts (dark blue regions) are present in the red pulp, and germinal centres (pale blue) can be seen in the follicles; the T zones (which lack B cells) remain unstained. The image is kindly provided by Jennifer Marshall and relates to the study Marshall et al. (pp. 3506–3512) in which it is shown that Ig class-switch recombination during extrafollicular responses occurs at the B blast rather than the plasmablast stage.
iNKT cells in diabetes: The good, The bad and the balance
Invariant natural killer T (iNKT) cells are innate-like T lymphocytes highly conserved in mice and humans. Type 1 diabetes (T1D) is an autoimmune disease caused by the destruction of insulin-producing pancreatic beta cells. Studies in mouse models have demonstrated the protective role of iNKT cells in the development of T1D. Recently, a new subset of iNKT cells producing high levels of the pro-inflammatory cytokine IL-17 has been identified (iNKT17). In this issue, Simoni et al. show that the non-obese diabetic (NOD) mouse, which spontaneously develops T1D, exhibits a larger iNKT17 cell population as compared with non-autoimmune C57BL/6 mice. iNKT17 cells infiltrating the pancreas of NOD mice are locally activated and produce IL-17. Contrary to the protective role of CD4+ iNKT cells, CD4− iNKT cells, containing an iNKT17 cell population, exacerbate diabetes in an IL-17-dependent manner. Therefore, the balance between protective and deleterious iNKT cells is a key parameter controlling autoimmunity.
Vaccine vector types and combinations determine T-cell quality
Different pathogens stimulate different innate responses, which in turn lead to distinct qualities of the elicited T cells. T-cell quality plays a key role in orchestrating immune responses and delivering the ultimate effector control of invaders. By the same token, different vaccine modalities employing the same transgenic antigen induce different qualities of transgene-specific T cells. Therefore, vaccines using benign viruses and bacteria as vectors are predisposed to prime T cells that control some pathogens better than others. Furthermore, vaccine combinations in heterologous prime-boost regimens not only enhance transgene-specific T-cell frequency, but allow for tuning of effector and memory T-cell qualities. In this issue, Hopkins et al. map the unique signatures of intercellular signaling molecules released by T cells elicited by six different HIV-1 vaccine candidates used singularly and in combination in mice. A truly rational vaccine regimen design awaits a more complete understanding of the workings of the immune system and its interactions with HIV-1.
Th1- and Th2-inducing DC profiles reveal quantitative differences in maturation
The maturation or activation of dendritic cells (DCs) is required to ignite efficient T-cell responses. The differences in the nature of pathogens with various pathogen-associated molecular patterns (PAMPs) have been proposed to direct either the Th1 or Th2 polarization of CD4+ T cells. In addition, inflammatory or infectious signaling pathways would be expected to raise different qualities of matured DCs. In this issue, Pletinckx et al. show that the maturation signatures and functionality of DCs matured by inflammatory signals (TNF) or pathogen-derived signals (Th2-inducing Trypanosoma brucei antigens) in mice are highly similar. Strikingly, the difference in regulated genes between the Th2-inducing DCs (160–466 genes) and LPS-matured Th1-inducing DCs (4969 genes) are mainly quantitative. Repetitive Th2 induction further shifts DC maturation to IL-10+ Tr1-like cells. Thus, the data indicate that simply the strength of DC maturation may dictate Th1/Th2 polarization.
How palmitoylation modulates the immune system
The human NKG2D receptor activates the immune response in lymphocytes, including CD8+ T cells and natural killer cells. In cells undergoing stress, such as transformation and viral infection, the expression of NKG2D ligands is induced. While binding of ligand to NKG2D triggers cytokine secretion and/or cytotoxicity, release of soluble ligand into the milieu downmodulates the receptor function of NKG2D. In this issue, Agüera-González et al. explore the role of a post-translational modification of the NKG2D ligand MICA on its expression and functional consequences. Two cysteine residues in MICA are identified whose mutation impedes palmitoylation of MICA. Recruitment of MICA to membrane microdomains of CHO cells, where it encounters the metalloprotease responsible for its shedding, is shown to be palmitoylation-dependent. Nonpalmitoylated MICA is released inefficiently from cells, whereas target CHO cells expressing the mutant MICA are recognized by NKG2D for cytotoxicity. These data indicate that post-translational modification of MICA differentially regulates protein shedding and immune recognition.
Does Nod2 have any T-cell intrinsic role?
Nod2 is a member of the family of cytosolic innate immune receptors called Nod-like receptors, and recognizes bacterial cell wall components. Mutations in the Nod2 gene are highly associated with an elevated risk of Crohn's disease. A recent article reported that Nod2 has a T-cell intrinsic role, and is important for the induction of Th1 immune responses and protection against Toxoplasma gondii infection. In this issue Caetano et al. show, in a collaborative work repeated in three independent laboratories, that Nod2 is not important for host defense against T. gondii. Nod2-deficient mice are fully capable of inducing Th1 immune responses and do not show enhanced susceptibility to T. gondii infection. Upon TCR stimulation in vitro, Nod2-deficient CD4+ T cells show normal activation, IL-2 production, proliferation and Th1/Th2 differentiation. These data strongly support the idea that Nod2 does not play any role in T-cell differentiation to Th1 and Th2 subsets.