Antonio Lanzavecchia
Institute for Research in Biomedicine, Bellinzona, Switzerland

Vaccination and Immunological Memory

Vaccination acts by inducing the clonal expansion and differentiation of antigen specific lymphocytes that persist for a lifetime as memory cells. Memory cells mediate two functions: they confer immediate protection in peripheral tissue and mount recall responses in secondary lymphoid organs. These functions are carried out by distinct cell types. In the B lymphocyte system protective memory is mediated by plasma cells that secrete antibodies, while reactive memory is mediated by memory B cells that are present in lymphoid organs and proliferate and differentiate to plasma cells in response to secondary antigenic stimulation. A similar division of labor has been recently defined for T lymphocytes. Protective memory is mediated by effector memory T cells (T_EM) that home to inflamed peripheral tissues and display immediate effector function, while reactive memory is mediated by a distinct subset of central memory T cells (T_CM) that retain lymph node homing receptors and high proliferative capacity in response to antigenic challenge.

I will review the experimental evidence supporting a “stem cell model” of immunological memory. Memory B cells and central memory T cells are intermediates of a progressive differentiation process, which have acquired the capacity to proliferate and differentiate in response to polyclonal stimuli such as cytokines, microbial products or bystander T cell help. While self renewing, memory B cells and central memory T cells continuously spill out plasma cells and effector T cells, thus replenishing those that turn over. Furthermore I will describe in detail the mechanisms that sustain serum antibody levels following vaccination and discuss the implications of these findings for vaccine design.

References:

1. Sallusto, F., D. Lenig, R. Forster, M. Lipp, and A. Lanzavecchia. 1999. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401:708-712.
2. Bernasconi, N.L., E. Traggiai, and A. Lanzavecchia. 2002. Maintenance of sero- logical memory by polyclonal activation of human memory B cells. Science 298:2199- 2202.