Persistence and responsiveness of immunologic memory in the absence of secondary lymphoid organs

Secondary lymphoid organs (SLOs) promote primary immune responses by recruiting naive lymphocytes and activated APCs. However, their role in the persistence or responsiveness of memory lymphocytes is unclear. We tested whether memory cells were maintained and could respond to challenge in the absence of SLOs. We found that influenza-specific CD8 cells in the lung acquired a memory phenotype, underwent homeostatic proliferation, recirculated through non-lymphoid tissues, and responded to and cleared a challenge infection in the complete absence of SLOs. Similarly, influenza-specific virus-neutralizing antibody was generated and maintained in the absence of SLOs. Inducible bronchus-associated lymphoid tissue (iBALT) was also formed in the lungs of previously infected mice and may provide a niche for the maintenance of memory cells at the local level. These data show that SLOs are dispensable for the maintenance of immunologic memory and directly demonstrate the utility of local tissues, such as iBALT, in secondary immune responses.