β1 Integrin Is Critical for the Maintenance of Antigen-Specific CD4 T Cells in the Bone Marrow but Not Long-Term Immunological Memory

Abstract

The long-term maintenance of memory CD4 T cells promotes protective immunity against future pathogen reinfection. As a site rich in survival cytokines, the bone marrow is proposed to be a critical niche for the survival of memory CD4 T cells. We demonstrate that endogenous, polyclonal Ag-specific CD4 T cells rapidly enter and are recovered long-term from the bone marrow following i.v. infection with Listeria monocytogenes. β1 integrin-deficient CD4 T cells also populate the bone marrow early following an infection, but their numbers in this site rapidly decline. This decline was not caused by increased death of T cells lacking β1 integrin but rather by reduced retention in the bone marrow after the primary immune response. The loss of memory CD4 T cells from the bone marrow does not lead to a loss of the predominant source of memory CD4 T cells in the spleen or the ability to mount a memory response. Thus, β1 integrin-dependent maintenance of memory CD4 T cells in the bone marrow is not required for long-term CD4 T cell memory.