Cell-mediated immunity in cutaneous disease

Microvascular Endothelial Cell Culture.

“…There was no binding of B lymphocytes. In several dermatoses including graft vs host disease, lupus erythematosis, and others, the principal intraepidermal lymphocytes present are of the T-cytotoxic/suppressor phenotype accompanied by increased HLA-DR expression [43], The findings that niicrovascular endothelial cells express HLA-DR in the presence of interferon gamma both in vivo and in vitro, that the adherence of PBML to endothelial cells is stimulated by interferon gamma, and that the immunophenotype of cells bound to microvascular endothelial cells reflects the same immunophenotypes types that are observed in the skin in inflammatory diseases, suggests that this tnodel may provide a basis for further fanctional studies ofthe mechanisms by which skin tnicrovascular cells influence PBML localization and recirculation in the skin.…”

Current understanding of the aetiology and clinical implications of cutaneous graft-versus-host disease

“…Inevitably, much ofthe available information has come from animal studies. Alloreactive cytotoxic T lymphocytes (CTL) seem to be neither necessary nor sufficient to induce acute lethal GVHD, which is thought to be mediated mainly by alloreactive donor T-suppressor cells which potentiate infection; the 'stimulatory' features of chronic GVHD, including production of autoantibodies characteristic of systemic lupus erythematosus, are thought to be mediated by donor alloreactive T-helper cells {see review by Breathnach & Katz, 1985a). These findings do not exclude a role for CTL in epithelial injury.…”

“…It is also not known exactly why the skin should be such a major target organ in GVHD, and which cells are the primary target for destruction. In addition to class I major histocompatibility complex (MHC) antigens, murine epidermal cells express certain unique skin-specific transplantation antigens such as Skn and Epa-i which are capable of inducing allograft rejection, and which may be of relevance in regard to the first point {see review by Breathnach & Katz, 1985a). Homologous skin-specific antigens have not as yet been identified in humans.…”

“…With regard to the second point, it has been suggested that stem cells in the basal layer of rete ridges, or their early progeny, may be specific targets, as a result either of osmotic fragility or of expression of early differentiation antigens (Sale et al, 1985). An alternative viewpoint is that Langerhans cells (LC), which are the only cells in normal epidermis which express class II MHC (Ia, immune response-associated, HLA-DR) antigens, may be a particular target for destruction in cutaneous GVHD, since Ia antigen is a major stimulatory determinant in GVHD, and since LC have an important function in allograft rejection and are the critical stimulator cells in the in vitro allogeneic epidermal cell-lymphocyte reaction {see review by Breathnach & Katz, 1985a). Keratinocytes might then be damaged by an 'innocent bystander' effect as a result of lymphokine release (Snover, 1984).…”

“…Given that cutaneous GVHD is essentially seen only in a few specialized centres, why should this dermatological rarity continue to receive so much attention in the literature? The reason, of course, is that GVHD in its acute and chronic forms shares clinical, histological and immunological features with several important lymphocyte-mediated skin diseases (Saurat, 1981;James & Odom, 1983), and provides a unique biological model for the study of the immunopathology of epidermal-lymphocyte interactions (Breathnach & Katz, 1985a). Three recent papers report on immunohistochemical changes in the skin following therapeutic bone marrow transplantation in humans (Atkinson et al, this issue;Dreno et al, 1986;Lever et al, this issue).…”