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Nickel (Ni) inhibits lymphoproliferative responses. Proliferation was performed on PBMC of 20 controls and 10 patients with Ni allergy. NiSO4 was used at a concentration of 0.1mM. PHA was added at a concentration of 5 μg/ml. Cells were incubated for 5 days and proliferation assessed by CFSE staining. At 0.1mM Ni strongly reduced (>40%) PHA-induced proliferation. The inhibition decreases in a dose-dependent manner and response to PHA is restored at 20 mM Ni. Ni alone induces small ( Strong inhibition was also observed in preliminary experiments with tuberculin purified protein derivative (PPD) stimulated PBMC. Staining for CD8 on CFSE cultures showed that PHA response was due to both CD8 and CD4 cells. Ni increased % of CD4 cells and decreased the % of CD8 cells. PPD response was predominantly a CD4 response, with Nickel reducing the % of CD4 cells at higher concentations, while unaffecting the CD8. Ni inhibits IL-6 production essential to normal PHA response. The addition of 10–100 IU of IL-6 and/or IL-2 to the cultures did not affect Ni inhibition of PHA proliferation. Addition of IL-6 increased CD25+ cells. Our data suggest that Ni induced inhibition of PHA response is due to steric interference between PHA and its cellular ligand. Further studies will clarify the precise mechanism of Ni mediated inhibition of immune responses and its the role in the pathogenesis of Ni allergy.