Figure 2.

Intrinsic changes in memory CD4 T cells which enhance their response to activation. There are a number of factors that can contribute to the distinct responses of memory CD4 T cells as compared to their naïve counterparts. T cell receptor (TCR) triggering can be enhanced in two ways: in polyclonal populations, the cells with the highest affinity for the antigen can come to dominate the response (1) alternatively, or in addition, the CD3 TCR-signaling complex is clustered more effectively in memory than naïve CD4 T cells (2). Intracellular signaling molecules are also altered: memory CD4 T cells contain more Zap 70 than naïve T cells (3) and TCR activation leads to increased phosphorylation of the MAPK, p38 (4). Changes in cell surface proteins, such as chemokine receptors (5) and integrins (6), affect cell migration and location enabling memory CD4 T cells to migrate rapidly to inflamed sites or reside permanently in pathogen-targeted tissues. Changes in gene transcription before and following T cell reactivation are also evident. Epigenetic differences between naïve and memory CD4 T cells enable more rapid transcription of effector molecules, such as cytokines, thereby accelerating the control and clearance of pathogens (17, 97–101).