TNFα Interrupts Antigen-Presenting Function of Langerhans Cells by Two Mechanisms: Loss of Immunogenic Peptides and Impairment of Antigen-Independent T Cell Clustering

Abstract

In vitro and in vivo experiments suggest that TNFα disturbs the antigen presenting function of epidermal Langerhans cells (LC), and contributes to the well known immunosuppressive effect of low-dose UVB irradiation. Presenting function of LC is impaired by low dose UVB.1,2 The UVB effect was shown to be mediated - at least in part - by TNFα. Simon et al.3 have shown that UVB irradiation converts LC to cells which can induce antigen-specific anergy in TH1 clones. Grabbe et al. demonstrated that LC cultured in the presence of TNFα were less effective in conveying protection from tumor in an adoptive transfer model.4 Our own data indicate that TNFα distorts the maturation process of LC in culture.5 Antigen processing appears not to be affected by TNFα but the capacity to stimulate resting T cells in the mixed leukocyte reaction is greatly impaired.6 We have, therefore, studied the effect of TNFα on murine LC in more detail by examining antigen processing and retention as well as on T cell binding.