期刊
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
卷 9, 期 9, 页码 559-570出版社
CARDEN JENNINGS PUBL CO LTD
DOI: 10.1016/S1083-8791(03)00288-X
关键词
acute graft-vcrsus-host disease; cytokeratin 15; target cells
资金
- NCI NIH HHS [CA 40358] Funding Source: Medline
- NHLBI NIH HHS [HL 55593] Funding Source: Medline
The identity of cells within squamous epithelia that represent primary targets in acute graft-versus-host disease (GVHD) has been an enigma. Murine effector T cells implicated in the alloresponse by Vbeta complementarity-determining region-3 spectratype analysis were detected with a Vbeta-specific monoclonal antibody within discrete microdomains of tongue (lingual) squamous epithelium. These microdomains, termed rete-like prominences (RLPs), are similar to the rete ridges of human skin. Cells forming the basal layer of RLPs and of human skin rete ridges were shown to express a distinctive pattern of keratin expression defined by antibodies to cytokeratin 15 (K15). In experimental murine GVHD elicited across minor histocompatibility antigen barriers (miHA), early lesions involved selective apoptosis and loss of K15(+) staining within lingual RLPs. An in vitro organ culture model designed to investigate target cell injury by short-term exposure to tumor necrosis factor-alpha and interleukin-1beta, mediators relevant to GVHD, showed a similar pattern of apoptosis and loss of K15(+) reactivity within RLPs. In aggregate, these findings establish a novel cytoskeletal marker for target epithelial subpopulations that should facilitate evaluation of mechanisms of host cell injury in GVHD. These data may also enable the development of therapeutic approaches to abrogate disease at the level of target cell blockade. (C) 2003 American Society fir Blood and Marrow Transplantation.
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