Cross-Reactivity of Human Nickel-Reactive T-Lymphocyte Clones with Copper and Palladium

Abstract

Twenty Ni-reactive T-lymphocyte clones were obtained from eight different donors and analyzed for their ability to cross-react with other metals. All Ni-reactive T-lymphocyte clones were CD4+CD8- and recognized Ni in association with either HLA-DR or -DQ molecules. Based on the periodic table of the elements, the metals Cr, Fe, Co, Cu, and Zn from the same horizontal row as Ni, and Pd and Pt from the same vertical row, were selected to study T-lymphocyte clone cross-reactivity. Distinct cross-reactivity patterns were found that could be divided into three major groups: Ni-reactive T-lymphocyte clones i) cross-reacting with Cu, ii) cross-reacting with Pd, or iii) without cross-reactivity. Major histocompatibility complex class II-restriction patterns of Cu- and Pd-induced proliferative responses did not differ from those for the Ni-induced responses. In vitro cross-reactivities with Cu and Pd may be favored by their bivalency and location next to Ni in the periodic table, and the similarity of these metals to Ni in binding to histidine residues of peptides in the pocket of major histocompatibility complex class II molecules. The present findings suggest that Cu and Pd hypersensitivities, which are occasionally observed in Ni-allergic patients, may be due to cross-reactivities at the T-cell clonal level rather than to concomitant sensitization.

Clinical immunology Th1 and Th2 cytokine profile of CD4 and CD8 positive peripheral blood lymphocytes in nickel contact dermatitis

“…Data regarding such correlations are lacking, a study investigating IFN-γ production in response to nickel challenge has also failed to demonstrate any correlation between IFN-γ and patch test scores, IL-5 however was shown to exhibit a strong correlation with nickel patch test scores [18]. Nickel has been shown to exhibit cross reactivity to palladium with regards to T cell recognition of these sensitizing agents [37]. Data from a recent study in agreement with the pervious findings have not only revealed induction of a predominant Th2 response by nickel and palladium challenge but a strong correlation between Th2 response and skin patch test scores was also observed in individuals sensitized against the respective metals [38].…”

Mechanisms of immunosensitization to metals (IUPAC Technical Report)

“…Many patients with Ni 2+ sensitivity also have Co 2+ sensitivity, but this may reflect concomitant sensitization rather than cross-reactivity. As noted above, cross-reactivity of Ni 2+ -reactive T-cell clones is seen with Cu 2+ and Pd 2+ , but not with Co 2+ [30,31].…”

“…However, some Ni-specific T-cell clones cross-reacted in vitro with Cu and Pd, but not with Co, Cr, or Pt [30], indicating that true cross-reactivity can occur at the clonal level. Another study [31] confirmed clonal cross-reactivity with either Cu or Pd, but not Co or Cr, in CD4 + clones from eight patients. The authors noted the similar binding ability of Ni, Cu, and Pd to histidine residues of peptides that might be found in the pocket of MHC class II molecules (see Section 3).…”

“…In an early study [70], 6 of 354 subjects reacted to a Cu patch test; all were women with hand eczema, but none had apparent occupational exposure to Cu, and none wore a contraceptive intrauterine device. Cross-reactivity with Cu, of Ni-selective T-cell clones, is noteworthy [31]. Common protein-binding motifs for Ni, Pd, and Cu, such as the Asp-Ala-His sequence at the N-terminal of albumin, may be important.…”

Copper and its inorganic compounds [MAK Value Documentation, 2006]

“…As it was possible to stimulate part of the nickel-specific T cell clones from patients sensitized to nickel by copper(II) sulfate as well, in vitro investigations suggest a crossreactive relationship between nickel and copper (Moulon et al 1995, Pistoor et al 1995. After in vitro induction with nickel sulfate, it was possible to stimulate quite a number of T cell clones from persons not sensitized to nickel with copper chloride.…”