Recombinant Gamma Interferon Induces HLA-DR Expression on Cultured Human Keratinocytes

Abstract

In normal human epidermis, expression of HLA-DR antigen is restricted to Langerhans cells (LC) and acrosyringial epithelium. However, in diseases such as lichen planus and graft-vs.-host, HLA-DR antigen appears to be expressed by keratinocytes, although the exact source of the HLA-DR is unclear. Two possibilities are that (1) the HLA-DR is shed by neighboring immunocompetent cells, or (2) that the keratinocytes are synthesizing the antigen themselves. Recently, gamma interferon has been shown to induce HLA-DR biosynthesis and expression on human malignant melanoma cells lines and on normal vascular endothelium. We report here that pure recombinant human gamma interferon (100 units/ml) induces HLA-DR expression on 60-70% of cultured human adult keratinocytes depleted of LC within 2-4 days of culture as determined by fluorescence-activated cell sorter (FACS) analysis using monoclonal antibodies. No residual LC or lymphocytes could be detected in these cultures. This is the first demonstration of HLA-DR expression by cultured human keratinocytes. This expression may be of functional significance in antigen presentation and cell-mediated cytotoxicity involving the epidermis.

Immunohistochemical characterization of vascular endothelial cells in cutaneous T-cell malignancies with special references to heterogenous expression of surface antigens associated with monocytes and macrophages.

“…HLA-DR synthesis by keratinocytes has been demonstrated to be induced by interferon in vitro (5). The present study showed that occurrence of HLA-DR on keratinocytes was invariably linked to the presence of lymphocyte infiltrates, including T-lymphoma cells, which were also CD3-positive, HLA-DR-positive, predominantly CD4-positive and occasionally IL-2 receptor-positive, as previously reported by others (3,10).…”

HLA-DP as specific target for cellular immunotherapy in HLA class II-expressing B-cell leukemia

“…HLA-DP-reactive T cells administered at the time of SCT may result in both GVHD and GVL reactivity as a consequence of upregulated HLA-DP expression on non-hematopoietic cells caused by proinflammatory cytokines released as a consequence of tissue damage induced by the conditioning regimen or infections. 11,12 T-celldepleted SCT followed by the infusion of donor T cells at a later time point, however, may more selectively induce a GVL response when tissue damage is largely restored, and the expression of HLA-DP is anticipated to be restricted to hematopoietic cells. In this study we showed that resting FBs and most other non-hematopoietic cell lines did not express HLA-DP and were therefore not recognized by the T-cell clones.…”

“…However, HLA class II expression can be upregulated on various tissues after exposure to proinflammatory cytokines. 11,12 An anti-HLA class II immune response following HLA class II-mismatched SCT may therefore also result in GVHD if HLA class II molecules on nonhematopoietic tissues are upregulated as a consequence of the conditioning regimen or infections. 13 The results obtained from clinical transplantation studies concerning the impact of mismatching for different HLA alleles have led to the current standard that patient and donor are usually preferably matched for the HLA class II alleles HLA-DR and HLA-DQ in addition to the HLA class I molecules.…”

Expression of HLA-DR molecules by keratinocytes, and presence of Langerhans cells in the dermal infiltrate of active psoriatic plaques.

“…This correlation suggests that T cells are important in the generation of psoriatic plaques . IFN-y has been shown to induce HLA-DR expression by normal keratinocytes (35), as well as by other epithelial cells (36)(37)(38) . Recently (39), intradermal injection of recombinant IFNy into cutaneous lesions of patients with lepromatous leprosy has been shown to induce HLA-DR expression by keratinocytes.…”