The Interaction Among Effector, Regulatory, and Tγδ Cells Determines the Development of Allergy or Tolerance to...

Background/Objectives: Chromium, a common environmental and occupational sensitizer, frequently induces allergic contact dermatitis (ACD). This study investigates the role of CD4⁺ (T helper), CD8⁺ (T cytotoxic), regulatory (Tregs: CD4⁺CD25⁺ and CD8⁺CD25⁺), and gamma delta (Tγδ) T cells in chromium tolerance versus hypersensitivity. Methods: Six chromium-allergic patients and six healthy controls were recruited, confirmed via patch testing. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured, with chromium exposure and proliferation assays conducted. Specific T cell subtypes were isolated and analyzed for chromium-specific proliferative responses, cytokine production, and metabolic activity. Results: Chromium-allergic individuals exhibited broad proliferation across PBMC and T cell subsets, contrasting with restricted responses in controls. Treg cells in healthy subjects effectively suppressed T cell proliferation in response to chromium, while allergic individuals showed unmodulated T cell activity, indicative of impaired regulatory function. Cytokine analysis revealed elevated IL-2 and TNF-α but absent IL-10 in allergic patients. Metabolic assessments showed higher glycolytic activity in Tregs of healthy controls, suggesting enhanced regulatory potential. Conclusions: These findings highlight the importance of balanced effector and regulatory T cell interactions for chromium tolerance. Dysregulated Treg and Tγδ cell functions in allergic individuals may contribute to hypersensitivity, with implications for targeted therapeutic strategies to restore immune balance and reduce allergic responses in chromium-sensitive patients.