CD8 - TREAT · CD8+ T regs in allergen tolerance
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2006-12-01 → 2008-11-30
- EU contribution
- €173,831
- Participants
- 1
- Scheme
- EIF
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Results in brief
Final Activity Report Summary - CD8 - TREAT (CD8+ T regs in allergen tolerance)
Allergic diseases and asthma pose an important and increasing problem for approximately 40 % of the world population. These diseases seriously affect the life-quality of the patients and cause immense health care expenses, being sometimes even life threatening. Therefore, research that contributes to a better understanding of allergic diseases underlying mechanisms and to the development of therapies is of high public concern. The CD8 - TREAT project, supported by the Marie Curie activity of the European Union, was set up to improve therapy and prevention of allergic diseases by elucidating the immunological mechanisms underlying allergen tolerance. The principal idea was to invent treatment strategies that enhanced the organisms inherent capability to suppress inflammation. Currently, the treatments are mainly designed to control inflammation and disease symptoms. Thus, this project was intended to support suppression and to control immune responses in a more specific way instead of unspecific inhibition of inflammation. T cells with regulatory activity, the so called Treg cells, were shown to be of great importance for the control of immune responses to infectious agents as well as for the tolerance of harmless environmental antigens like allergens or of the body´s own constituents. Research which was performed at the Swiss Institute of Allergy and Asthma Research (SIAF) in Davos, Switzerland, during the last two years in the CD8 - TREAT project investigated the immune regulatory role of human CD8+ T cells. Our research work led to the identification of a new CD8+ T cell population with the characteristics of Treg cells in human tonsils. Because of their localisation at the gateway of the respiratory and alimentary tracts, tonsils were important for the discrimination between harmless and harmful potential pathogens. Surprisingly, cells expressing pro-inflammatory cytokines were also present in this regulatory population. Interestingly from a therapeutic point of view, it was possible to generate CD8+ T cells that possessed the capability to control other cells of the immune system. The project findings suggested that CD8+ Treg cells located in the tonsils were involved in the control of immune responses to up-taken antigens and might suppress other T cells even in a pro-inflammatory environment. However, further studies were needed to investigate how these cells contributed to tolerance. Relevant outcomes could lead to the development of immune modulating therapies in the future.
Data: CORDIS, © European Union
Project objective
Allergic diseases result from an unbalanced response of the specific immune system, generating allergen-specific IgE antibodies, which mediate various clinical symptoms, such as immediate type hypersensitivity. The disease severity correlates with the activity of CD4+ T cells.The existence of allergen-specific CD4+ Th2 cells, however, is not sufficient for allergy pathogenesis, since these cells are also found in healthy individuals. In contrast, allergen specific regulatory T cells (Tregs) occur at higher frequency than their effector counterparts in healthy individuals and are capable of suppressing proliferation and cytokine expression of Th1 and Th2 cells.Tregs are defined on the basis of their function, in contrast to Th1 or Th2 cells, which are characterized by their gene products. The exact definition of the Tregs phenotype is therefore often difficult. Recent evidence revealed that also CD8+ Tregs contribute to peripheral tolerance.However the contribution of these cells in allergic disease is unclear. We have preliminary evidence showing that CD8+ T cells play an important role in the allergen-specific responses. Aim of the proposal is to analyze the contribution of allergen-specific CD8+ T cells to the tolerance against allergens in healthy and allergic individuals.Therefore the impact of allergen-specific, effector versus regulatory CD8+ T cells in allergen-driven immune reactions will be investigated along with their crosstalk to CD4 subsets and the antigen presenting cells.We anticipate an advanced understanding of the cellular players in tolerance and pathogenesis of allergy and in turn new approaches in anti-allergic therapy.
Original text from CORDIS.
Participants
- SWISS INSTITUTE OF ALLERGY AND ASTHMA RESEARCH · DAVOSCoordinatorCity levelSwitzerland
Links
Data: CORDIS, © European Union