DNA damage and mutation: contributors to the age-related alterations in T cell-mediated immune responses?

ABSTRACT

The genetic material of our cells is susceptible to damage by a wide variety of extrinsic and intrinsic entities. The amount of genetic damage accumulated in vivo will depend upon an individual's ability to defend against and/or repair DNA damage. T cells in vivo have been shown to accumulate DNA damage and mutations over time. The accumulation of such genetic damage will occur in T cells possessing a 'naive' or a 'memory' phenotype. Since T cells are required to undergo extensive clonal expansion upon antigenic stimulation, DNA damage and mutations may result in a failure of T cells to proliferate, because of DNA damage-mediated cell cycle arrest; decreased rates of proliferation, as a consequence of selection in vivo against cells carrying certain mutations and/or apoptosis, triggered by critical levels of DNA damage. Thus, when T cells, containing critical levels of genetic damage, are required to undergo rapid clonal expansion in the presence of antigen, insufficient numbers of T cells may be produced and so the immune response would be sub-optimal. In this paper the possible contribution of DNA damage and/or mutation to the age-related alterations in T cell-mediated immune responses will be discussed.