Human T Cell Clones in Long Term Culture as Models for the Impact of Chronic Antigenic Stress in Aging

Graham Pawelec, Erminia Mariani, Rafael Solana, Rosalyn Forsey, Anis Larbi, Simona Neri, Olga Dela Rosa,

Yvonne Barnett, Jon Tolson, and Tamas Fulop

Monoclonal human T lymphocytes can be maintained untransformed in tissue culture by intermittent antigen restimulation in the presence of growth factors for only a finite period (which, however, varies greatly from clone to clone). This tissue culture model can be employed to examine many aspects of clonal expansion and contraction under conditions of chronic antigenic stress, such as that which occurs in vivo in the elderly (where herpes viruses represent an important chronic stressor), as well as in cancer. In this context, the model can be used for biomarker discovery at the genomic, proteomic, and functional levels, and to test remedial interventions of possible utility in vivo. Furthermore, the clonal characteristics of cells from donors of different ages and states can be compared using this model (cloning efficiency, mean longevity, maximum longevity, aging behavior, etc.). This chapter briefly describes techniques for the production and maintenance of human T cell clones, their growth characteristics and longevity in vitro, culture age-associated changes of parameters such as telomere lengths, DNA damage, surface molecules and so on, and the application of proteomic analyses to study this model of immuno-senescence in detail.

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