Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

Functional Modification of Epidermal Dendritic Cells by Topical Steroids to optimize Tolerogenic Potential of Immunotherapy for Type 1 Diabetes (#139)

Mohammad Alhadj Ali 1 , Stephanie Hanna 1 , Susan Wong 1 , Colin Dayan 1
  1. Cardiff University, Cardiff, United Kingdom

Introduction:

In humans, the use of the intradermal route has a specific advantage in peptide immunotherapy as skin dendritic cells are potentially accessible for both peptide immunotherapy and local treatment with agents able to maintain the tolerance state.

Aims and Objectives:

Our aim was to determine whether topical pretreatment of the skin with steroid has the potential to modulate the function of epidermal dendritic cells.

Methods:

Healthy volunteers received 0.05% Betamethasone twice daily for 4 days to the skin of the left arm. At day 5, volunteers had a suction blister raised at the treatment site and a second blister raised in the right arm (control). Epidermal cells from treated and untreated sites were used separately to stimulate Mixed Epidermal Cells Lymphocyte Reaction (MECLR) using PBMCs from healthy donor (B) and used also in a culture in combination with naive T cells from (B). T cells recovered from these cultures were added to a fresh MLR to test their suppressive capacity.

Results:
MECLR driven by epidermal cells from the steroid treated skin were lower than with cells from the untreated skin (P=0.001). MECLR responses were “normalized” to the MLR response and MECLR/MLR was also markedly reduced in the steroid treated arm compared with the ratio calculated from the control arm (P=0.008). T cells from culture with epidermal dendritic cells from the steroid treated skin tended to suppress MLR responses more than T cells induced by culture containing epidermal dendritic cells from the control skin.

Conclusion:

Pretreatment of the skin with steroids (Betamethasone) for a period of 4 days shows significant effects on epidermal dendritic cells function in the Mixed Epidermal Cells Lymphocyte Reaction. This study indicates the ability of steroid treated epidermal dendritic cells to induce T cells which are able to suppress the proliferation of autologous naïve T cells.