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M9550031.TXT
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1995-03-04
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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).