GAMMA_DELTA_IMMUNO · Gamma delta cells and immunosurveillance
6РП — Действия „Мария Кюри“
- Период
- 2004-04-01 → 2006-03-31
- Финансиране от ЕС
- 167 665 €
- Участници
- 1
- Схема
- EIF
Линиите свързват координатора с партньорите.
Накратко на български
Гама-делта Т-клетките се анализират за да се разбере как реагират на специфични протеини и метаболити при инфекции и рак. По-доброто познаване на тези механизми помага за подобряване на имунотерапията при пациенти с карциноми.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - GAMMA_DELTA_IMMUNO (Gamma delta cells and immunosurveillance)
Molecular analysis of gamma/delta T cell responses provides insight into carcinoma trial data. Human peripheral blood gamma/delta T cells expand dramatically in response to the microbial metabolite HMB-PP which characterises many infections. Gamma/delta cells also recognise phosphorylated 'activators', and stress antigens on transformed cells. These observations underpin the hypothesis that gamma/delta cells can compose a powerful, non-MHC restricted component of immunotherapy for infections and tumours. However, the cells' optimal application requires an improved molecular understanding of their responses. Here, array comparisons with CD8 alpha/beta T cells have identified several molecular signatures of gamma/delta T cells. Among them, tumour - necrosis-factor-related-apoptosis-inducing-ligand (TRAIL) is strongly upregulated specifically by T cell receptor (TCR) gamma/delta and interleukin (IL)-2 stimulation. In stage-four carcinoma patients, a gamma/delta-TCR agonist (zoledronate) plus IL-2, but not zoledronate alone, sustained TRAIL levels and correlated positively with clinical outcome. These data clarify the biology and emphasise specific clinical potentials of gamma/delta T cells. Distinct cytokine-driven responses of activated blood gamma/delta T cells: insights into unconventional T cell pleiotropy. Human gamma/delta T cells comprise a small population of peripheral blood T cells that in many infectious diseases respond to the microbial metabolite, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), and rapidly expand to up to 50 % of CD3+ cells. Although this transitional response is widely viewed as pro-inflammatory and/or cytolytic, the increasing evidence that different cytokines drive distinct effector functions in alpha/beta T cells provoked us to use cDNA microarrays to explore in more detail the potential pleiotropy of HMB-PP-activated gamma/delta T cells. The related cytokines, IL-2, IL-4, or IL-21 each drove proliferation and comparable CD69 upregulation but induced distinct effector responses that were also different from the prototypic responses of alpha/beta T cells. Thus, the Th1-like response to IL-2 also included IL-5 and IL-13 that conversely were lacking from the IL-4 response. IL-21 induced a lymphoid homing phenotype and high expression of the follicular B-cell attracting chemokine CXCL13/BCA-1, thus defining a novel candidate TFH-like cell, which may play an important, hitherto underappreciated role in driving humoral immunity early in infection. Their broad and unanticipated plasticity may permit gamma/delta T cells to bridge innate and acquired immunity in a variety of contexts. These findings enhance our understanding of the multi-faceted human gamma/delta Tcell compartment, and have implications for the ongoing clinical application of cytokines and gamma/delta TCR agonists.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Epithelia are potentially vulnerable to infection and environmentally induced mutation. Although there unwell-established ideas for how the immune system may protect epithelia, they fail to mention intraepithelialymphocytes (ells) that are one of the largest T cell compartments. Gamma delta cells contribute to a large part to these ells. The properties of gamma delta cells seem to place them midway the adaptive and innate immune response. The host laboratory has recently obtained evidence that gamma delta ells provide bothimmunoprotection and immunoregulation within epithelia: this proposal asks how. There are two aims: in the first, candidate genes will be identified by comparative Serial Analysis of Gene Expression (SAGE); in the second the contribution of particular genes to IEL activities in vitro and in vivo will be examined (e.g. by RNA interference).The results should provide a much-improved understanding of epithelial immunosurveillance.The experience profile of David Vermilion (e.g. NK cell background, experiences with ransoms, confocalmicroscopy and apoptosis assays) can clearly add value to the applied project. Equally clear are the benefits for David Vermilion to be gained from his participation in the proposed project Gamma delta cells andimmunosurveillance. He will be trained in advanced techniques like SAGE, he will learn to work with knockout animal models and he will acquire the RNA interference technique. Thus the experience of David Vermilion on the one hand and the training possibilities offered at the Laboratory of Adrian Heyday on the other hand, are complementary. This will result in a synergistic effect and therefore enhance the scientific excellence of the European Union.
Оригинален текст от CORDIS (на английски).
Участници
- KING'S COLLEGE LONDON · LONDONКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз