Low ICAM-1 expression in the epidermis of depigmenting C57BL/6J-mivit/mivit mice: a possible cause of muted contact sensitization.

The depigmenting C57BL/6J-mivit/mivit) (mivit/mivit) mouse, a congenic mutant of the C57BL/6 strain, exhibits an isolated, single immune deficiency. It is unable to mount a normal immune/inflammatory response upon epicutaneous application of DNFB or TNCB, although it does respond normally to oxazalone. The present investigations have been carried out to further study this deficiency. In vivo, C57BL/6 mice could be sensitized by the epicutaneous application of the hapten TNCB, the subcutaneous injection of hapten(TNBS)-conjugated C57BL/6, and hapten conjugated mivit/mivit epidermal cells. In the mivit/mivit mice, however, only subcutaneous injection of haptenized C57BL/6 epidermal cells caused an immune response. The response of these mivit/mivit mice could be documented only by adoptive transfer of splenic lymphocytes into naive C57BL/6 animals which then reacted to challenge doses of TNCB. These observations suggest that mivit/mivit epidermal cells can process and present and mivit/mivit T lymphocytes can react to the antigen. We postulated the presence of a deficient in vivo interaction between epidermal cells and T lymphocytes in the mivit/mivit mice. ICAM-1 is an important adhesion signal regulating epidermal cell/T-lymphocyte interaction. Its expression in mivit/mivit mice was studied using YN1/1 antibody against MALA-2, the murine counterpart of human ICAM-1. In contrast to C57BL/6 animals, the mivit/mivit epidermis essentially did not stain with the antibody after hapten challenge. In vitro after stimulation with TPA or IFN-gamma, the mivit/mivit epidermal cells expressed significantly lesser amounts of ICAM-1 than the C57BL/6 epidermal cells. Lower expression of ICAM-1 by mivit/mivit epidermal cells has also been demonstrated both by direct staining and by flow cytometry. The binding of lymphocytes to mivit/mivit epidermal monolayers, which were stimulated to express ICAM-1 by IFN-gamma, was decreased compared to that of C57BL/6 epidermal cells. We conclude that the muted contact sensitization response detected in vivo in the mivit/mivit mice at least partly results from lower expression of ICAM-1 and thus defective epidermal cell/T-lymphocyte interaction.