Pathogenic role of tonsillar lymphocytes in associated with HSP60/65 in Pustulosis Palmaris et Plantaris

Abstract

Objective We aimed to define role of tonsillar lymphocytes (TL) and immune cross-reactivity between bacterial-HSP65 and human-HSP60 in Pustulosis palmaris et plantaris (PPP), an intractable chronic disease characterized with pustules and cornification of palms and soles. Methods Two sets of crossover trials were designed by employing SCID mice model. In the first trial, mice were transplanted with tonsillar lymphocytes and skin-grafts from PPP patients (TL group). In the second trial, mice were transplanted with tonsillar lymphocytes from PPP patients and injected with recombinant human HSP60. Control groups were designed for each step. Comparisons were performed for immunologic analyses including infiltration of CD4+ lymphocytes in skin-grafts by immunostaining, and levels of anti-HSP65-IgG and cytokines in mice sera by enzyme-linked immunosorbent assay (ELISA). Results In TL group, infiltration of CD4+ lymphocytes in skin-grafts were significantly higher than mice transplanted with blood lymphocytes ( p < 0.05), while anti-HSP65-IgG levels in sera showed non-significant tendency to increase in the TL group. CD4+ cells and anti-HSP65-IgG levels were also well-correlated with each other in TL group ( p < 0.01). Besides, anti-HSP65-IgG levels were significantly correlated with cytokine levels (IL-6, IFN-γ) in mice sera ( p < 0.01). We found strong expression of HSP60 in PPP lesions. Finally, HSP60-stimulation in mice transplanted with TL from PPP patients induced significantly higher anti-HSP65-IgG levels in serum compared to control groups including mice without HSP60-stimulation or peripheral blood lymphocytes-transplanted mice or transplanted with TL from control patients ( p < 0.05). Conclusion Our results indicate the pathogenic role of TL and immune cross-reaction between human-HSP60 and bacterial-HSP65 in PPP.