CD8(+) T-cell selection, function, and death in the primary immune response in vivo

The primary immune response to Epstein Barr virus (EBV) is characterized by striking proliferation of EBV-specific CD8(+) T cells. In this study we ha ve investigated the clonal composition and functional properties of the cel ls mediating this primary response and have analyzed the mechanisms that co ntrol the downregulation of the primary response and the selection of memor y cells. We show that massively expanded T-cell clones often dominate the p rimary antigen-specific T-cell response. Despite the enormous extent of exp ansion, the virus-specific T cells express high levels of intracellular per forin and are potently cytotoxic. They are, however, functionally heterogen eous in their ability to secrete proinflammatory cytokines, with subpopulat ions of the antigen-specific T cells being hyporesponsive. The primary resp onse is closely regulated, and the majority of cells are programmed to die via a cytokine-rescuable pathway leaving only small populations of memory T cells surviving. Comparison of the clonal composition of primary and memor y responses in vivo shows that the clones that dominate the primary respons e are relatively heavily culled during the downregulation of the primary re sponse and the establishment of T-cell memory.