In this issue

Abstract

AbstractCover imageThis issue's cover image depicts thymus ontogeny in mice associated with changes in the distribution patterns of Spatial and keratins by thymic epithelial cells, taken from Saade et al. (pp. 530–538). In this article, the authors explore the expression of the Spatial gene during thymus ontogeny and in the adult thymus, and demonstrate that in the medulla RANK signals regulate Spatial expression through the transcription factor Aire. Images were acquired with the Leica TCS SP5. magnified imageWorms get hormonalpp. 406–416Infections with parasitic helminths have been very informative when it comes to developing our understanding of Th2 immunity at mucosal sites. Although many researchers observe gender‐dependent differences in immune responsiveness, few have studied this phenomenon mechanistically. In this issue, Hepworth et al. investigate the role of sex hormones during the development of Th2 immunity to infection with the gastrointestinal nematode Trichuris muris. Interestingly, the authors show that androgens (such as testosterone) but not estrogens potently suppress the generation of protective Th2 immunity. This study identifies a complex interplay between the immune system and the host factors, such as hormones, and demonstrates that effective immunity can be profoundly influenced under such conditions. magnified imageProtective immunity in tuberculosis – not without IL‐18pp. 396–405On the 25th 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. magnified imageMeasles virus‐specific T cells: Kill or be killedpp. 388–395Measles is a highly contagious viral disease, killing approximately 200 000 children each year. The virus is lymphotropic and infects high percentages of B and T cells via its cellular receptor CD150. Paradoxically, virus‐specific T cells can be either viral targets or effector cells mediating viral clearance. In this issue, de Vries et al. examine whether specific CD4+ or CD8+ T cells can inhibit measles virus replication. The authors infected B cells with a recombinant measles virus expressing GFP, added specific T cells and monitored virus dissemination. Using this model, the authors demonstrate that measles virus‐specific CD8+ T‐cell clones and primary CD8+ T cells isolated from convalescent measles patients suppressed virus replication in autologous or HLA‐matched B cells. Specific CD4+ T cells not only were incapable of inhibiting virus replication, but were also more readily infected by the virus. The authors speculate that a similar approach may be used to study functional T‐cell responses as potential correlates of protection in vaccine trials. magnified imageA new drug for modulating T‐cell differentiation in autoimmune conditionspp. 460–469Natura‐alpha is a newly developed immune‐regulatory agent that has been shown to exert potent therapeutic activity against colitis in the murine model. In this issue, Glatigny et al. study the effects of Natura‐alpha on collagen‐induced arthritis, a murine model that mimics many of the symptoms of rheumatoid arthritis. The authors examine the effect of the compound on both adaptive and humoral immune responses. Although the exact effects of the compound on T‐helper differentiation pathways remain to be elucidated, this study suggests that Natura‐alpha modulates autoimmune inflammation by targeting the Th1/Th17 pathway. This study implies that the effects of Natura‐alpha may also extend to other autoimmune diseases involving Th1/Th17 cells. magnified imagep53, a double‐edged sword in the fight against cancerpp. 559–568Among the many conundrums that face immunologists is the fact that many pro‐apoptoic molecules that suppress tumour development, also repress the generation of T‐cell responses that are needed for effective anti‐tumour immunity. Therefore, while a lack of apoptotic machinery on the one hand promotes tumoroigenesis, on the other it also has the potential to help generate enhanced T‐cell responses against tumors. In this issue, Singh et al. report that unlike wild‐type T cells, T cells lacking the tumor suppressor p53 do not undergo apoptosis when the TCR is engaged in the absence of costimulation. Furthermore, p53−/− mice mount an effective and potent cytotoxic T‐cell response against transplanted tumors and successfully clear the tumour. Thus, p53 functions not only as a tumor suppressor but also as an opposing role in dampening T‐cell responses, and thus preventing the generation of effective anti‐tumor T‐cell immunity. This study suggests that manipulation of p53 for cancer therapy requires a careful balancing act. magnified image