Identification and Characterization of Circulating Naïve CD4+ and CD8+ T Cells Recognizing Nickel

Allergic contact dermatitiscaused by contact sensitizers is a T-cell-mediated inflammatory skin disease. The most prevalent contact allergens is nickel. Whereas, memory T cellsfrom nickel-allergic patients are well-characterized, little is known concerning nickel-specific naive T-cellrepertoire. The purpose of this study was to identify and quantify naive CD4+ and CD8+ T cellsrecognizing nickelin the general population. Using a T-cellpriming in vitro assay based on autologous co-cultures between naive T cellsand dendritic cells loaded with nickel, we were able to detect a naive CD4+ and CD8+ T-cellrepertoire for nickelin 10/11 and 7/8 of the tested donors. We calculated a mean frequency of 0.49 nickel-specific naive CD4+ T cellsand 0.37 nickel-specific naive CD8+ T cellsper million of circulating naive T cells. The activation of these specific T cellsrequires MHC molecules and alongside IFN-γ production, some nickel-specific T-cellswere able to produce granzyme-B. Interestingly, nickel-specific naive CD4+ and CD8+ T cellsshowed a low rate of cross-reactivity with cobalt, another metallic hapten, frequently mixed with nickelin many alloys. Moreover, naive CD4+ T cellsshowed a polyclonal TCRβ composition and the presence of highly expanded clones with an enrichment and/or preferentially expansion of some TRBV genes that was donor and T-cellspecific. Our results contribute to a better understanding of the mechanism of immunization to nickeland propose the T-cellpriming assay as a useful tool to identify antigen-specific naive T cells.