Expression of lymphotoxin‐αβ on antigen‐specific T cells is required for dendritic cell function

Abstract

The lymphotoxin (LT) pathway has been shown to be important in T cell responses and DC homeostasis/activation. LTαβ is a TNF family member upregulated on activated T cells and its receptor, LTβR, is constitutively expressed on DC. Elucidating the role of LTβR signaling in DC function is complicated by the expression of LTβR on both lymphoid stromal cells and DC. Here we have used two methods for inhibiting LTβR signaling. In the first we use an in vivo adoptive transfer system where the expression of the LTβR ligands is manipulated only on the Ag‐specific T cells that interact with and condition Ag‐bearing DC. Using this approach we demonstrate a novel requirement for the LTαβ for optimal DC conditioning during an immune response against protein antigen.In the second system, we have manipulated the expression of LTβR on DC using a mixed bone marrow chimera approach. Here we report a requirement for DC‐intrinsic LTβR signaling for the optimal upregulation of CD86. In addition, DC‐intrinsic LTβR signaling influences DC accumulation in the inflamed LN. Together these data identify a fundamental role for DC‐intrinsic LTβR signaling during T cell immune responses. Funding from CIHR (JLG and LSD) and MS Society of Canada (LSD) supported this research.