Immunohistology of graft-versus-host disease mediated skin lesions and its correlation to a large granular lymphocyte surface phenotype and function

Abstract

Skin lesions of five patients presenting with acute and chronic Gvhd after bone marrow transplantation were analyzed on frozen tissue sections using selected monoclonal antibodies against various T-cell determinants and HLA-antigens in order to define immunological phenomena characteristic for cutaneous damage seen in various GvHD states. Four of these patients showed marked increase of a certain T-cell subpopulation positive for HLA-D region products in the upper dermis. A considerable number of these T-cells seemed to show cytotoxic reactivity on the basal cell layers of the epithelium and to correlate with the appearance of an OKT4-, OKT8+, HLA-DR+ T-cell subset in the peripheral blood presenting natural killer (NK) cell like activity on various targets. Ia antigen expression on keratinocytes observed in one patient with chronic GvHD could result from a rapid and irregular turnover of epidermal cells affected by continuous stimuli of these T-cells. Further immunological studies on skin biopsies of patients with different states of GvHD and autoimmune diseases may lead to valuable diagnostic criteria for an early and accurate assessment of various skin lesions in patients after bone marrow transplantation.

Mononuclear cell subpopulations in the skin defined by monoclonal antibodies after HLA-identical sibling marrow transplantation

“…In agreement with our study, they found no or only occasional T cells (defined by OKT3) in the majority (five of nine), no B cells (defined by surface membrane immunoglobulin staining) and T8 -I-cells to be commoner than T4 -I-cells in those in whom T cells were present. Muller et al (1982) using immunoperoxidase, described three patients with acute GVHD, but did not speeify the time post-transplant of the biopsies, nor use antibodies defining the helper-inducer and cytotoxic-suppressor T cell subset. Increased T cells, expressing HLA-D region products, were noted in the epidermis and at the dermo-epidermal junction.…”

Immunological monitoring of bone marrow transplant recipients

“…There is, however, another explanation for this finding. As activated lymphocytes are seen in the dermal-epidermal junction of the skin and in the epithelial areas of the liver and the gut during aGVHD (4-6, 8, 26) and as the LGL frequently contribute to the skin lesions (27), the depletion of these cell populations from the blood may be interpreted as compartmentalization of these cell populations to the target organs (28).…”

Renal, Major Histocompatibility Complex Antigens and Cellular Components in Rapidly Progressive Glomerulonephritis Identified by Monoclonal Antibodies

“…Immunoperoxidase labeling was performed on 4-to 5-pm thick cryostat sections exactly as described in detail earlier [14]. In all experiments control sections were incubated with supernatant of the inactive mouse monoclonal reagent W6/32.HK as a first anti body layer to reveal unspecific labeling.…”