Forschungs- & Entwicklungsinformationsdienst der Gemeinschaft - CORDIS

In vitro models of T cell immunosenescence

We believe that the in vitro modelling of the process of clonal expansion and contraction, or lack of it, under chronic stimulation can contribute to further definition and/or confirmation of biomarkers predictive of T cell dysfunction and provide some ideas on possible remediation in vivo.

These approaches still focus on the use of cytokines and anti-oxidants which might not present too much of an ethical and logistical hurdle in the elderly. The data currently suggest that, at least for CD4 cells, certain types of anti-oxidant supplementation and manipulating the cytokine environment can extend the lifespan of T cells in vitro, and that zinc supplementation can enhance heat shock protein upregulation, thereby possibly providing more protection from stress.

There are intriguing hints that stress resistance and integrity of cell signalling and DNA repair capacity change somewhat with age in culture but that the most marked differences are seen between donors from whom TCC are derived: the older the donor, the better the cell integrity, even at very high PD.

This applied to hsp expression, to microsatellite instability and DNA repair and other important parameters such as membrane fluidity and CD28 signalling. Thus, monoclonal T cells derived from progenitor cells were in general less stable than those from adults, and nonagenarians and centenarians were the most stable. This apparently counter-intuitive finding is presumably an expression of the strong selective pressure for survival to 90-100 years of the donors. Genomic and proteomic screening of TCC derived from different donors cultured for shorter or longer periods provided data that were consistent with this idea.

These results all point towards intrinsic genetic programs in successfully aged donors, which maintain superior immune responsiveness under conditions of chronic antigenic stress. The search for these genetic factors, includes cytokine and cytokine receptor polymporphisms as well as immunogenetic studies on HLA in populations and families. These data need to be integrated with current and future projects specifically addressed to the genetics of healthy ageing.

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University of Tübingen
Waldhörnlestr. 22
72072 Tübingen
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