In this issue

Abstract Cover image This issue's cover image shows immunofluorescent staining of endothelial cells for microtubules (red) and vascular endothelial cadherin (green). The image was taken from the article Endothelial IQGAP1 regulates efficient lymphocyte transendothelial migration by Nakhaei‐Nejad et al . (pp. 204–213), in which the authors examine the role of IQGAP1, an adaptor protein that binds to filamentous‐actin and microtubules at interendothelial junctions, during lymphocyte transendothelial migration.It pays to have an immune mother pp. 113–116 Currently, the archaic fear of a circulating, possibly deadly infection has raised its head in the form of H1N1 influenza. Although we have learned how to artificially vaccinate against influenza and many other infectious agents, we still do not understand very well how natural herd immunity is maintained in general. In this issue, Navarini et al . show a new aspect of how newborns with maternal antibody protection can directly form lifelong immunity against poxviruses. Infant mice were challenged with a high dose of Vaccinia virus directly after birth. Mice survived this infection only if they received neutralizing maternal antibodies. Interestingly, these mice stayed immune to poxvirus infection for their whole life, indicating that an early virulent infection can function as an effective vaccination. Therefore, clearly, attenuation of infection as a result of maternal‐derived antibodies has both short‐ and long‐term survival advantages.Treg‐mediated control of cytotoxic and pro‐inflammatory γδ T cells pp. 61–70 On the 25 th anniversary of γδ T cells' accidental discovery, γδ T cells remain poorly understood; however, the potent anti‐tumor and pro‐inflammatory functions of γδ T cells are well documented. In this issue, to further explore the interaction of γδ T cells with other components of the immune system, Gonçalves‐Sousa et al . show that mouse Treg efficiently suppress γδ T cell responses both in vitro and in vivo . Treg use cell‐to‐cell contact to “anergize” γδ T cells, thus preventing their cytotoxicity and cytokine (IFN‐γ, IL‐17) secretion functions upon activation. This suppression, however, can be partially reversed using anti‐GITR antibodies, which may be relevant for clinical application. In fact, as human Treg have also been shown to inhibit γδ T cell responses to TB antigens, the combined modulation of γδ and Treg functions should be considered in future immunotherapeutic protocols.Egr2 and positive selection: Protect and survive pp. 232–241 Following thymocyte‐positive selection, a signalling pathway triggered by TCR binding to antigen‐MHC dictates changes in gene expression that lead to survival, differentiation and maturation. In this issue, Lawson et al . show that the transcription factor Egr2, which is rapidly induced following TCR ligation, can protect positively selected thymocytes from apoptosis. This is due, at least in part, to Egr2 activating the IL‐7‐mediated survival pathway. Prior to positive selection, the IL‐7 signal is attenuated by the presence of Socs1, which blocks the activation of downstream survival factors, including Bcl2. The authors show that induction of Egr2 not only enhances IL‐7R expression but may also be the molecular switch that turns off Socs1 after TCR signalling, thereby allowing Bcl2 expression. Expression of Egr2 following positive selection directly links the initial TCR signalling event to a key survival pathway.Survival advantage of Ccr 5‐deficiency pp. 267–278 Chemokine receptors have crucial roles in leukocyte trafficking. Previous studies using chemokine receptor‐deficient mice analyzed defects in the recruitment of specific leukocyte subpopulations, i.e . quantitative effects. Qualitative effects not reflected by changes in leukocyte numbers were frequently overlooked. In this issue, Dehmel et al. describe the analysis of a fully MHC‐mismatched renal transplantation model performed in WT and Ccr5 −/− mice. Although the number of macrophages was comparable in transplanted kidneys from both recipients, there was a marked difference with respect to the activation status. During the chronic rejection phase, several markers for alternatively activated macrophages were strongly upregulated in Ccr5 −/− recipients. Similar results were obtained with splenocytes from unchallenged Ccr5 −/− mice, suggesting that Ccr5 ‐deficiency favors alternative macrophage activation in general. These findings may also be relevant for other diseases with macrophage participation and may explain the significantly increased human renal transplant survival observed in CCR5‐D32 homozygous patients.Treg have a new therapeutic target: VEGFR2 pp. 197–203 CD25 + FOXP3 + CD4 + Treg play critical roles in immune tolerance against selfantigens including many tumor antigens. In order to improve the efficacy of cancer immunotherapy, therefore, many investigators are attentively searching Tregspecific molecules that control the number and/or function of Treg. In this issue, Suzuki et al . show that Treg, especially FOXP3 high Treg, selectively express the novel molecule VEGFR2 on their cell surface. These VEGFR2 + Treg exist in several tissues including PBMC, malignant effusion‐derived lymphocytes and lymph nodes. In addition, VEGFR2 + Treg suppress the proliferation of CD4 + T cells. he data strongly suggest that VEGFR2 is a valuable target for controlling the quantity and quality of Treg, especially Treg with high suppressive activity.