Cancer Immunity 3 Suppl 2:2 (2003)

Vaccination and immunological memory

Antonio Lanzavecchia

Institute for Research in Biomedicine, Bellinzona, Switzerland

Abstract

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, Lenig D, Forster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 1999; 401: 708-12. (PMID: 10537110) [PubMed]

2. Bernasconi NL, Traggiai E, Lanzavecchia A. Maintenance of serological memory by polyclonal activation of human memory B cells. Science 2002; 298: 2199-202. (PMID: 12481138) [PubMed]