Function and regulation of memory CD4 T cells

The development of peripheral naive CD4 T cells is dependent on the success of positive selection of immature T cells in the thymus. Only thymocytes that express a T cell receptor (TCR) capable of recognizing self-MHC with low affinity are selected for survival and differentiation into mature naive T cells. Although the TCR of naive T cells has to maintain self-tolerance, it also propagates naive CD4 T cell proliferation on recognition of appropriate foreign peptide associated with MHC class II on antigen-presenting cells (APCs). Naive CD4 T cells that successfully engage foreign peptide undergo further differentiation that leads to the maturation of a select few into the memory T cell pool. Although the requirements that lead to memory T cell development are currently not known, functional changes have been described that are thought to be associated with the greater efficiency with which memory T cells respond to antigen. This article will discuss differences associated with signaling through the TCR of naive and memory CD4 T cells and describe unique control mechanisms imposed on memory CD4 T cells that are likely to have arisen to counterbalance the altered TCR signaling.