The cellular basis of T-cell memory.

Abstract

One of the major characteristics of the immune system is its ability to react more quickly and more intensely on the second exposure to an antigen. This characteristic, usually referred to as immunologic memory, was first observed in studies of antibody production in vivo (reviewed in 1). The secondary, or anamnestic, response to an antigen not only results in the production of increased levels of antibodies, but these antibodies also generally have a higher affinity for antigen compared to those antibodies produced during the primary response (2). Memory at the B-cell level is generally accepted as the result of selection and specific expansion of clones secreting high affinity antibody molecules (3, 4). Molecular studies suggest that somatic hypermutation of antibody variable-region genes during the primary response may be responsible for the occurrence of B cells express­ ing high affinity receptors (reviewed in 5). However, the differentiation pathway involved in the generation of memory B cells is still poorly understood. In particular, it is not clear how, in the primary response, some of the B cells differentiate into terminal plasma cells and others into memory cells. While there is ample evidence that immunologic memory also involves T cells, our understanding of the molecular and cellular basis of T-cell secondary responses is quite limited. Following early studies dem­ onstrating that cytolytic T lymphocytes (CTL) are not necessarily terminal cells but may differentiate, at least in vitro, into cells exhibiting the expected properties of memory cells (6), attempts have been made to define quan­ titative and qualitative differences between memory T cells and T cells that have not yet been stimulated by antigen (which are often designated as