antigen presentation, cellular immunity, dendritic cells, Langerhans cell, ligand, T lymphocyte activation
DCs are critical for initiating immunity. The current paradigm in vaccine biology is that DCs migrating from peripheral tissue and classical lymphoid-resident DCs (cDCs) cooperate in the draining LNs to initiate priming and proliferation of T cells. Here, we observe subcutaneous immunity is Fms-like tyrosine kinase 3 ligand (Flt3L) dependent. Flt3L is rapidly secreted after immunization; Flt3 deletion reduces T cell responses by 50%. Flt3L enhances global T cell and humoral immunity as well as both the numbers and antigen capture capacity of migratory DCs (migDCs) and LN-resident cDCs. Surprisingly, however, we find immunity is controlled by cDCs and actively tempered in vivo by migDCs. Deletion of Langerin+ DC or blockade of DC migration improves immunity. Consistent with an immune-regulatory role, transcriptomic analyses reveals different skin migDC subsets in both mouse and human cluster together, and share immune-suppressing gene expression and regulatory pathways. These data reveal that protective immunity to protein vaccines is controlled by Flt3Ldependent, LN-resident cDCs.
Anandasabapathy, N., R. Feder, S. Mollah, S. -W Tse, M. P. Longhi, S. Mehandru, I. Matos, et al. 2014. "Classical Flt3L-Dependent Dendritic Cells Control Immunity to Protein Vaccine." Journal of Experimental Medicine 211 (9): 1875-1891