Neoantigen Expression in Steady-State Langerhans Cells Induces CTL Tolerance
Helen Strandt, Douglas Florindo Pinheiro, Daniel H. Kaplan, Dagmar Wirth, Iris Karina Gratz, Peter Hammerl, Josef Thalhamer and Angelika Stoecklinger
Abstract:
The skin hosts a variety of dendritic cells (DCs), which act as professional APC to control cutaneous immunity. Langerhans cells (LCs) are the only DC subset in the healthy epidermis. However, due to the complexity of the skin DC network, their relative contribution to either immune activation or immune tolerance is still not entirely understood. To specifically study the function of LCs in vivo, without altering the DC subset composition in the skin, we have generated transgenic mouse models for tamoxifen-inducible de novo expression of Ags in LCs but no other langerin+ DCs. Therefore, this system allows for LC-restricted Ag presentation to T cells. Presentation of nonsecreted OVA (GFPOVA) by steady-state LCs resulted in transient activation of endogenous CTL in transgenic mice. However, when these mice were challenged with OVA by gene gun immunization in the contraction phase of the primary CTL response they did not respond with a recall of CTL memory but, instead, with robust Ag-specific CTL tolerance. We found regulatory T cells (Tregs) enriched in the skin of tolerized mice, and depletion of Tregs or adoptive experiments revealed that Tregs were critically involved in CTL tolerance. By contrast, when OVA was presented by activated LCs, a recallable CTL memory response developed in transgenic mice. Thus, neoantigen presentation by epidermal LCs results in either robust CTL tolerance or CTL memory, and this decision-making depends on the activation state of the presenting LCs.
The open access article can be found  here.
The article is being featured by the „In This Issue“ section in the September 01, 2017 issue of The Journal of Immunology. „In This Issue“ highlights articles considered to be among the top 10% of articles published in The Journal.

Reviewed by Hans Brandstetter