Lightning Talk & Poster Presentation CD1-MR1 Workshop 2025

Investigating the role of CD1a and CD1d in Nickel Allergic Contact Dermatitis  (#17)

Aoife Clancy 1 , Anne-Marie Tobin 2 3 , Fei Lai 2 , Derek G Doherty 4 , Niamh M O'Boyle 1
  1. School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
  2. Department of Dermatology, Tallaght University Hospital , Dublin, Ireland
  3. School of Medicine, Trinity College Dublin, Dublin, Ireland
  4. Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland

Allergic contact dermatitis (ACD) is a delayed-type IVa hypersensitivity reaction driven by allergen-specific T cells, leading to symptoms such as redness, itching, and blistering1. Previous studies have shown that CD1a can present contact allergens like benzyl cinnamate to T cells, promoting cytokine production2. This study investigates whether CD1a and CD1d can present the metal allergen nickel to T cells in PBMCs from healthy and nickel-allergic donors.

PE-labelled CD1a and CD1d tetramers (NIH tetramer facility), loaded with nickel (II) sulfate hexahydrate, were used to stain PBMCs from healthy donors and nickel allergic donors, and analyzed by flow cytometry. T cell responses to nickel presented by CD1a and CD1d were assessed by incubating PBMC from nickel-allergic patients or healthy donors with CD1a and CD1d-transfected C1R and HeLa cells, loaded with nickel (II) sulfate hexahydrate, and measurement of intracellular IFN-γ, TNF-α, and IL-2 production by flow cytometry.

Nickel-loaded CD1a tetramers recognized significantly more T cells in both donor groups than unloaded tetramer controls. Nickel-treated CD1a-expressing C1R cells induced greater IFN-γ, TNF-α, and IL-2 production by PBMCs than unloaded CD1a+ C1R cells or CD1a-negative C1R cells. PBMC from nickel-allergic patients contained higher numbers of nickel/CD1a tetramer-positive T cells than PBMC from healthy donors and these cells more frequently produced IFN-γ and TNF-α in response to nickel-pulsed CD1a+ C1R cells. Additionally, a notable increase in multifunctional T cells, producing both IFN-γ and TNF-α, was observed in allergic donors compared to healthy donors. Nickel loaded into CD1d tetramers also recognised significantly more T cells than unloaded tetramers. Nickel-treated CD1d-transfected HeLa cells induced TNF-α and IL-2 production more frequently in nickel-allergic PBMCs compared to control PBMCs, but no increase in IFN-γ production was observed.

These results demonstrate that nickel presentation via CD1a and CD1d can activate T cells in nickel-allergic individuals, suggesting a role for CD1-mediated pathways in the pathophysiology of nickel ACD.

  1. 1.Rustemeyer, T.; van Hoogstraten, I. M. W.; von Blomberg, B. M. E.; Scheper, R. J., Mechanisms of Allergic Contact Dermatitis. In Kanerva’s Occupational Dermatology, John, S. M.; Johansen, J. D.; Rustemeyer, T.; Elsner, P.; Maibach, H. I., Eds. Springer International Publishing: Cham, 2020; pp 151-190
  2. 2. Nicolai, S.; Wegrecki, M.; Cheng, T. Y.; Bourgeois, E. A.; Cotton, R. N.; Mayfield, J. A.; Monnot, G. C.; Le Nours, J.; Van Rhijn, I.; Rossjohn, J.; Moody, D. B.; de Jong, A., Human T cell response to CD1a and contact dermatitis allergens in botanical extracts and commercial skin care products. Sci Immunol 2020, 5 (43)