Enhanced responsiveness to antigen contributes more to immunological memory in CD4 T cells than increases in the number of cells.

Although immunological memory is characterized by both an increase in the frequency of antigen-specific T cells and a qualitative change in the pattern of their subsequent response, it is not clear which of these components is more significant in the overall enhanced response to secondary stimulation. To address this question for the CD4+ T-cell response, T-cell receptor (TCR) Tg T cells were adoptively transferred to normal syngeneic mice that were immunized with the relevant peptide. After the initial expansion of TCR Tg T cells, the size of the subsequent memory population of T cells was approximately the same as the size of the starting population, independent of the number of TCR Tg cells initially transferred. This result was not caused by redistribution of memory cells into non-lymphoid tissues, although the relative frequency of antigen-specific T cells in these sites was increased after immunization. The fraction of the antigen specific TCR Tg cells that responded by production of either interleukin-2 or interferon-gammain vitro was substantially higher after immunization. Thus, the increased frequency of functionally responsive T cells was primarily caused by a higher fraction of responding T cells, rather than a substantial increase in the absolute number of antigen specific CD4+ TCR Tg T cells.