Expression of Fas ligand in Langerhans' cell histiocytosis: A case report of a boy with multisystem involvement

Abstract

Previous reports of patients with Langerhans' cell histiocytosis have shown characteristics of osteolytic lesion, visceral involvement and organ dysfunction. We report a 2-year-old boy who was diagnosed as Langerhans' cell histiocytosis with a prominent hepatomegaly. X-Radiogram, computed tomography and magnetic resonance imaging revealed the osteolysis of the right iliac bone, the absence of the left eighth rib as well as the right mandible, and an enhancing mass in the left cerebellum. The data of radiography were highly suggestive of Langerhans' cell lineage. The presence of large CD1a-positive mononuclear cells associated with inflammatory cells in peripheral blood smear and bone marrow aspirate further confirmed the diagnosis. In addition, expressions of S100, CD25, CD68, CD80, CD86, and Fas ligand were identified on these cells by immunocytochemical staining. The results indicate that although these cells are activated Langerhans' cells, progression of the disease and the bone destruction could be mediated by the overt FasL expression of the cells.

Immature dendritic cells kill ovarian carcinoma cells by a FAS/FASL pathway, enabling them to sensitize tumor-specific CTLs

“…Strong expression of FasL mRNA as well as protein was found in the ascites‐derived DCs, although the cell surface‐located FasL was expressed only at low levels. Similar findings were described in several reports on macrophages/monocytes, which were shown to express high levels of intracellular FasL12–14 that could be released in an active, soluble form following activation of these cells 12, 13. As we were able to block the DC‐mediated lysis of ovarian carcinomas by anti‐Fas IgG1 mAb, we conclude that the FasL is functionally involved in the lysis of Fas‐expressing tumor cells.…”

“…A FasL‐mediated mechanism has been demonstrated in physiologic and pathophysiologic events, including activation‐induced cell death (AICD) of lymphocytes,29 immune privilege and escape of tumors from the immune system30 and active defense mechanisms of the host against infected or transformed cells, thereby inducing apoptosis in target cells 31, 32. Functionally active FasL was recently also described in human monocytes or macrophages,12, 13, 33 Kuffer′s cell15 and Langerhans cells,14 which were able to induce FasL‐mediated apoptosis in target cells. Also, in a subset of spleen DCs in mice, functional FasL molecules were found to be expressed 34…”

“…Unlike Fas, the surface expression of FasL appears to be more restricted and often requires cellular activation 10. Highly purified DCs grown from normal mouse bone marrow in medium with GM‐CSF and IL‐4,11 human monocytes/macrophages,12, 13 Langerhans cells14 and Kuffer′s cells15 could express FasL mRNA and FasL. Furthermore, monocytes/macrophages can trigger apoptosis in target cells mediated by FasL upregulated by cellular activation 13, 14.…”

“…Highly purified DCs grown from normal mouse bone marrow in medium with GM‐CSF and IL‐4,11 human monocytes/macrophages,12, 13 Langerhans cells14 and Kuffer′s cells15 could express FasL mRNA and FasL. Furthermore, monocytes/macrophages can trigger apoptosis in target cells mediated by FasL upregulated by cellular activation 13, 14. In addition, the progression of apoptosis not only involves the interaction and activation of the cascade of proteases related to FasL5 but is also influenced by several other intracellular proteins such as those of the Bcl‐2 superfamily and some tumor suppressor gene products, including p53 and IRF‐1 16…”

The tolerogenic molecule CD95‐L is expressed on the plasma membrane of human activated, but not resting, Langerhans' cells.

“…Although this study does not address whether CD95‐L expressed on the LC membrane is functional, an obvious possibility is that, as CD95‐L‐expressing lymphoid cytolytic cells trigger apoptosis of CD95‐expressing target cells (56), and because the expression of CD95‐L on the surface of a even non‐lymphoid cell is sufficient to make that cell cytolytic (51,52), CD95‐L‐expressing LC may be cytolytic against a variety of CD95‐expressing cells. In fact, LC of LC‐histiocytosis express CD95‐L, and bone destruction was mediated by the overt CD95‐L expression by these activated LC (57). In addition, because LC are involved in initiation of specific T‐cell responses (17,18,58), an intriguing possibility could be that CD95‐L‐expressing LC might trigger cytolysis of T cells specifically interacting with them, because T cells are known to express CD95 on the surface and even increase such CD95 expression when activated (48–50).…”