Abstract

Maintaining memory T cells is critical to the success of vaccination and T cell survival is heavily influenced by costimulatory molecules, amongst which, the tumour necrosis factor super family members OX40 and CD30 are clearly important for CD4 T cells. Since lymphoid tissue inducer (LTi) cells, the key hematopoietic cell type responsible for lymph node formation, constitutively express high levels of both OX40L and CD30L in the adult, but not the embryo (when lymph nodes form), we investigated whether these cells were involved in memory CD4 T cell survival in vivo. Mice deficient in RORg, which lack LTi cells, were unable to generate memory antibody responses upon challenge. Furthermore, antigen-specific memory CD4 T cells failed to survive in RORg^-/- mice. To specifically test whether LTi cells were the RORg-dependent population required, memory CD4 T cells were transferred into chimeric mice comparable except for the presence or absence of LTi cells. The survival of these memory CD4 T cells was entirely LTi cell dependent. Whilst naive CD4 T cell survival was unaffected by the absence of LTi cells, the persistence of memory phenotype cells arising from homeostatic proliferation, was also LTi-dependent. Agonistic anti-OX40 Abs could rescue memory T cell survival in the absence of LTi cells, indicating that provision of OX40L is one mechanism by which LTi cells support CD4 T cell survival. In summary, we demonstrate that LTi cells support memory CD4 T cells in vivo identifying a novel and important role for these innate lymphoid cells.