Document 0031
 DOCN  M9550031
 TI    CD8+ activated T lymphocytes produce an in vitro skin graft-versus-host
       reaction in an organotypic skin culture model.
 DT    9505
 AU    Jakic-Razumovic J; Sale GE; Beauchamp MD; Storb R; Sandmaier BM; Program
       in Transplantation Biology, Fred Hutchinson Cancer; Research Center,
       Seattle, WA 98104.
 SO    Transplantation. 1995 Jan 15;59(1):69-78. Unique Identifier : AIDSLINE
       MED/95141370
 AB    We adapted organotypic skin cultures to the dog as a model for skin
       graft-versus-host reaction (GVHR) to explore the relative roles of T
       cells and cytokines. To produce GVHR, activated lymphocytes from bulk
       mixed leukocyte cultures (bMLC) from 2 dog leukocyte antigen-unrelated
       dogs were injected into organotypic skin cultures. Additionally, effects
       of separated CD4+ and CD8+ activated lymphocytes as well as
       cytokine-containing (TNF alpha and IFN gamma) supernatants from bMLC
       were studied. Noninjected cultures as well as cultures injected with
       autologous (cultured and uncultured) lymphocytes and allogeneic
       uncultured lymphocytes served as controls. The unseparated
       bMLC-activated cell populations induced histopathological changes
       similar to in vivo skin GVHR along with very prominent class II antigen
       expression on keratinocytes. Separated CD8+ cells were directly involved
       in tissue damage by producing necrosis of epidermis at the site of
       injection, with less class II antigen expression on keratinocytes, and
       predominantly distributed intraepidermally. CD4+ cells, located mostly
       in the dermal regions, induced prominent class II antigen expression on
       keratinocytes, but no histological changes of GVHR. High levels of TNF
       alpha and IFN gamma were found in the supernatant of allogeneic bMLC
       cultures, although when the supernatant was injected into the
       organotypic skin cultures, keratinocytes failed to express surface class
       II antigen and histologically did not show changes of skin GVHR. This
       study demonstrated that organotypic skin cultures can serve as a model
       for studying the etiology of GVHR, and indicated direct involvement of
       CD8+ cells in tissue damage.
 DE    Animal  Cell Transplantation  CD4-Positive
       T-Lymphocytes/METABOLISM/*TRANSPLANTATION  CD8-Positive
       T-Lymphocytes/METABOLISM/*TRANSPLANTATION  Dogs  Graft
       Rejection/*IMMUNOLOGY/PATHOLOGY  HLA-D Antigens/IMMUNOLOGY  Interferon
       Type II/BIOSYNTHESIS  Keratinocytes/IMMUNOLOGY/PATHOLOGY  Necrosis
       Skin/*IMMUNOLOGY/PATHOLOGY  Skin Transplantation/*IMMUNOLOGY  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Tissue Culture
       Transplantation, Autologous  Transplantation, Homologous  Tumor Necrosis
       Factor/BIOSYNTHESIS  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).