Contact Hypersensitivity is Suppressed After Sensitisation by Dinitrofluorobenzene of Early Stage Iso-Skin Grafts

Abstract

Isologous free skin grafts were applied to the backs of BALB/c mice and contact hypersensitivity studied by epicutaneous application of DNFB (2,4-dinitro-1-fluorobenzene) to the grafted skin. In the first experiment, the grafted skin was sensitised and the elicitation reaction assessed by measuring the ear swelling after five days. Sensitisation was not successful until two weeks after grafting. In such non-responding animals, re-sensitisation with DNFB on the ungrafted skin area was also unsuccessful, indicating the establishment of immunological tolerance. This tolerance was considered antigen-specific, as re-sensitisation with oxazolone was successful. In the second experiment, spleen cell suspension, both untreated and treated in vitro with antiThy 1.2, antiLyt 1.2, and antiLyt 2.2 antibody, from non-DNFB-responding mice was transferred into normal mice. Subsequently these mice were sensitised with DNFB. Sensitisation was not successful in the untreated group or in those treated with antiLyt 1.2 antibody. On the other hand, the groups treated with antiThy 1.2 and antiLyt 2.2 antibody did become sensitised. These results indicate that the unsuccessful delayed hypersensitivity of the grafted skin was caused by suppressor T cells. In addition, the density of epidermal Langerhans cells was reduced in the early stages of skin grafting and morphological abnormalities were present. From these results, we conclude that contact sensitisation during the early stage of grafting skin not only produces suppression of ear swelling but also induces antigen-specific tolerance. These results also suggest that the suppression depends on the antigen-specific suppressor cells and that acquirement of tolerance is associated with a reduction in the number of epidermal Langerhans cells in the grafted skin and abnormalities in their structure.

IL-10-Producing Langerhans Cells and Regulatory T Cells Are Responsible for Depressed Contact Hypersensitivity in Grafted Skin

“…To confirm the previous observation by Yasuda et al (1996) and to further examine whether the suppression of CHS by sensitization through skin grafting is a local or systemic phenomenon, mice were sensitized with picryl chloride (PCl) through grafted dorsal skin or non-grafted abdominal skin after skin graft implementation (on day 7 after operation). When PCl was applied to the grafted area for sensitization, the ear swelling challenge response was significantly lower than that of the positive control without skin graft (Figure 1).…”

“…Clinical observations have suggested impaired immunity in grafted skin (Doiurnon et al, 2001), and the lack of dermatitis on the graft is empirically known; therefore, some immunological alterations are thought to take place in the graft. Only one study has demonstrated that murine contact hypersensitivity (CHS) to a hapten cannot develop upon sensitization through full-thickness grafted skin (Yasuda et al, 1996).…”