Assessing Cd8 T Cell Number and Dysfunction in the Presence of Antigen

CD8 T cells proliferate and differentiate into cytokine-secreting cytolytic effectors on encounter with viral antigens. As virus is cleared the activated T cells undergo apoptosis, but some survive and enter the memory pool where they persist indefinitely, slowly dividing in a relatively quiescent state until reactivation on reexposure to the antigen 1. The dynamics of this whole process can be variable and change as a consequence of the antigen load, the diversity of the available T cell repertoire, and the age of the host. During persistent infections, T cells and antigen coexist in an interactive environment, leading to a continued evolution of T cells that often become dysfunctional. New technologies with avidin-linked MHC tetramers, chimeric IgG–MHC dimers, and peptide-induced intracellular cytokine assays have allowed for the identification of multiclonal populations of antigen-specific T cells and are now showing how T cells can be heterogeneous in their expression of surface antigens and exist in dramatically different functional states. Under certain conditions, antigen-specific T cells may lack effector activity, and under other conditions, fully functional T cells may lack reactivity with MHC tetramers or dimers, leading one to conclude that monitoring T cell responses by a single technique may lead to misconceptions of the nature of an ongoing T cell response.