Langerhans' cells are depleted in chronic graft versus host disease.

Abstract

Aims-To measure Langerhans' cells in skin of patients treated by bone marrow transplantation who developed chronic graft versus host disease (GvHD); to determine whether the reduction in Langerhans' cells resulted directly from the GvHD or from other factors, such as the immunosuppressive regimens used in bone marrow transplant patients. Patients and methods-Lesional and nonlesional skin specimens from nine patients with lichen planus-like lesions and three patients with sclerodermoid lesions were studied. Control skin specimens were taken from three patients undergoing breast reduction surgery. The number of Langerhans' cells/mm2 and the area of Langerhans' cells as a percentage of total epidermis were measured by counting cells labelled with antihuman CDla. Results-A significant reduction in Langerhans' cell area and number were found in specimens with lesions (area 3.5%; number 507/mm2) compared with specimens without lesions (8.42%; 2375/mm2).In contrast, Langerhans' cell area and number in skin without lesions were similar to controls (10.26%; 29681mm2). Conclusions-Langerhans' cells were significantly reduced in skin with lesions of chronic GvHD but not in skin without lesions from the same patient, suggesting that the reduction is a direct consequence of GvHD and not linked to immunosuppressive drugs or late effects of conditioning regimens. In long term bone marrow transplant recipients, Langerhans' cells are derived mainly from the donor cells; therefore, this result suggests the occurrence of autoreactive phenomenon in

Langerhans Cells and T Cells in Oral Graft versus Host Disease and Oral Lichen Planus

“…Our results support these studies. However, Aractingi and collaborators report a reduction of skin LC in cGVHD [40]. Compared to healthy oral mucosa we found increased numbers of CD1a expressing LC and cells with LC morphology expressing CD80 and CD86 in both cGVHD and OLP, suggesting an ongoing local uptake and presentation of allo‐ or autoantigens.…”

Induction of GVHD-Like Skin Disease by Passively Transferred CD8+ T-Cell Receptor Transgenic T Cells into Keratin 14-Ovalbumin Transgenic Mice

“…LC work as sentinels in skin and subserve an important role in T-cell-mediated skin diseases, such as contact dermatitis (Tamaki et al, 1981) and atopic dermatitis (Taylor et al, 1991). In GVHD, it is well known that epidermal LC disappear from the skin lesion (Lampert et al, 1982;Aractingi et al, 1997), suggesting their activation and migration to the regional LN. In our model system, expansion of OT-I cells began on day 4 and then the swelling of the footpads and ears and histological changes occurred starting on days 6-7 and LC decreased in density from the epidermis when these K14-mOVA Tg mice were analyzed 7-10 d after OT-I T-cell transfer (data not shown).…”

Lichen sclerosus and eosinophilic fasciitis as manifestations of chronic graft-versus-host disease: Expanding the sclerodermoid spectrum

“…58,60,61 Although the number of Langerhans cells is decreased in chronic GVHD and increased in LS, antigen presentation by keratinocytes is thought to be involved in the pathogenesis of both conditions. 16,58,62 In addition to alloreactive T lymphocytes, autoreactive CD4 1 T lymphocytes arising in the setting of defective thymic deletion (possibly related to thymic damage by GVHD and/or conditioning regimens and age-related decline in thymic function) may play a role in the development of chronic GVHD. 16,49,52 Investigators have observed a high prevalence of autoantibodies to a variety of cell surface and intracellular antigens in both chronic GVHD and LS.…”