In vivo effects of interferon-γ and anti-interferon-γ antibody on the experimentally induced lichenoid tissue reaction

Abstract

We investigated the in vivo effect of recombinant interferon-gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha) treatment of mice on the development of the delayed-type hypersensitivity (DTH) reaction and lichenoid tissue reaction (LTR) following the local injection of cloned autoreactive T cells. Both the DTH reaction and the LTR were significantly enhanced by pretreatment with IFN-gamma, but not with TNF-alpha. Induction of class II MHC antigens on keratinocytes was not essential for the enhancement by IFN-gamma. Administration of anti-IFN-gamma antibody reduced the DTH reaction and LTR, although complete inhibition was not observed with our treatment regimen. The ability of IFN-gamma to increase the number of the cloned T cells invading the epidermis in vivo, is in keeping with our previous observation that IFN-gamma treatment of cultured keratinocytes markedly increased the adherence reaction between T cells and keratinocytes in vitro.

Psoriasis and Lichen planus: Coexistence in a Single Patient

“…Indeed, in the lesion of lichen planus, HLA-DR and ICAM-1 antigens were strongly expressed on kcratinocytcs, thus indicating local production of IFN-y. The notion that damage to the basal cells seen in lichen planus may be mediated in part or at least perpetuated by IFN-y is strongly supported by our experimental evidence that murine lichenoid tissue reaction induced by local adoptive transfer of cloned CD4+T cells was enhanced by pretreatment of recipient mice with IFN-y, but not with tumor necrosis factor [ 18]. On the other hand, IFN-y has been reported to have some therapeutic activity in certain patients with psoriasis [ 19], although the magnitude of this effect appears to be much smaller than expected from its antiproliferative activities in vitro.…”

“…What is the most probable com mon factor? Recently, a central role of IFN-y released from activated T cells in the pathogenesis of lichen planus has been proposed by Morhenn [17] and us 112, 13,18]. Indeed, in the lesion of lichen planus, HLA-DR and ICAM-1 antigens were strongly expressed on kcratinocytcs, thus indicating local production of IFN-y.…”

Altered expression of extracellular matrix proteins and integrins in oral lichen planus (OLP)

“…Whereas the integrins in OLP showed a more non-specific pattern typical for a chronic inflammatory reaction, the most intense changes of the ECM pattern as compared with normal oral mucosa were noted in the subepithehal connective tissue, resembling the pattern of severe inflammation observed in gingivitis (34). This loss of ECM proteins, especially in the atrophic variant of OLP, is probably due to cytokines released from immunocompetent cells such as interferon y and TNFalpha that induce the expression of collagenases and that are found in LP (3,35). The prominent loss of ECM proteins in the atrophic type of OLP, not only in the upper but also in the deeper connective tissue, leads to complete architectural destruction compared with normal oral mucosa and suggests that the autoimmune reaction is not primarily targeted to oral keratinocytes but to an unknown antigen in the connective tissue stroma.…”

Leprosy: accessory immune system as effector of infectious, metabolic, and immunologic reactions

“…In tuberculoid and indeterminate leprosy, TNF‐α molecules act on epidermal basal keratinocytes, which produce ICAM‐1 and, in association with melanocytes, create a cytokine cellular barrier. This functional barrier prevents CD4+ Th‐1 and CD8+ lymphocytes from contacting antigenically primed suprabasal Langerhans cells and induces the early release of IL‐2 and IFN‐γ these, in turn, produce hydropic degeneration of basal keratinocytes, apoptosis with colloid body formation, and dyskeratotic cells in the stratum spinosum 129–134 …”