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  • Classical Flt3L-dependent dendritic cells control immunity to protein vaccine.

Classical Flt3L-dependent dendritic cells control immunity to protein vaccine.

The Journal of experimental medicine (2014-08-20)
Niroshana Anandasabapathy, Rachel Feder, Shamim Mollah, Sze-Wah Tse, Maria Paula Longhi, Saurabh Mehandru, Ines Matos, Cheolho Cheong, Darren Ruane, Lucas Brane, Angela Teixeira, Joseph Dobrin, Olga Mizenina, Chae Gyu Park, Matthew Meredith, Björn E Clausen, Michel C Nussenzweig, Ralph M Steinman
ABSTRACT

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 Flt3L-dependent, LN-resident cDCs.

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