Maintenance of the T Lymphocyte Pool by Inhibition of Apoptosis: A Novel Strategy of Immunostimulation?

Throughout development T lymphocytes are constantly confronted with a series of vital options. First, T cells can decide to either ignore an antigen or to become activated upon antigenic stimulation. Second, T cell activation may have rather disparate consequences, T lymphocytes may become productively activated to proliferate, differentiate or exert an effector function. Alternatively, they can become activated in an abortive or aberrant fashion, leading to anergy or apoptosis. The option that the T cell will choose among these possibilities is not only dictated by the conformation and concentration of the antigenic peptide/MHC complex, but depends also on a series of further circumstances: the particular context of cosignais perceived via receptors interacting with the antigen-presenting cell (APC), bystander cells (Ding and Shevach 1994), cell matrix proteins and soluble factors (cytokines and hormones), and the particular subpopulation to which the responding cells belong and their differentiation stage and (pre-) activation state. In this sense, T cells function as semiotic entities; they integrate signals from a complex universe as a function of their previous experiences to act in a quantitatively and qualitatively graded, rather than all-or-nothing, fashion.