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Experimental graft versus host disease in the (BN x LEW) F1 rat hybrid: an immunohistochemical study of early disease in oral mucosa.


Oral Dis. 1996 Mar;2(1):2-10. Unique Identifier : AIDSLINE MED/97116847

OBJECTIVE: To study the initial cellular events in oral mucosa (tongue) of experimental hyperplastic GVHD, in order to increase our understanding of the possible pathogenic mechanisms that may be shared with eg mercury (and other drug)-induced immunological reactions. MATERIALS AND METHODS: GVHD was induced by one i.v. injection of 0.5-1 x 10(8) BN spleen cells into (BNxLEW)F1 hybrid rats. The pre-onset stages of the developing semiallogeneic GVHD were investigated in tongue mucosa by immunohistochemistry and monoclonal antibodies. RESULTS: No detectable tissue infiltrates were found 24 h post induction. The pioneer cells appeared at day 3 and were RTIB+/CD2+ and RTIB1-/CD45 (240 kD)-/ EDI-/CD45RC-. At day 3, there was also a visible increase in spleen and lymph node size. Between day 3 and 7, there was a statistically significant increase of CD2+, RTIB+, TCR-alpha beta+, CD4+ and CD8+ cells, but no increase of NKR-PI+ cells. At day 10 there were focal accumulations of CD8+ and NKR-PI+ cells in subepithelial c.t. and in the basal parts of the adjacent epithelium. Animals not sacrificed earlier, showed signs of disease onset at day 11-14. CONCLUSIONS: The early inflammatory infiltrate in this GVHD model consists of activated T cells of donor origin. We suggest, that these originally 'naive' cells migrate initially into lymphoid tissue and following an activation (day 3) enter host's peripheral tissue. Here, (allo-) antigen in constitutively RTIB1 (and EDI) expressing connective tissue dendritic cells may be immune targets of the primed T cells. Such interaction may lead to focal inflammation (increase of CD2+, RTIB+, TCR-alpha beta+, CD4+ and CD8+ cells) and to secondary epithelial damage executed by CD8+ and NKR-PI+ lymphocytes.

Analysis of Variance Animal Antibodies, Monoclonal Cell Transplantation Cytotoxicity, Immunologic CD8-Positive T-Lymphocytes/IMMUNOLOGY Female Graft vs Host Disease/IMMUNOLOGY/PATHOLOGY Immunohistochemistry Killer Cells, Natural/IMMUNOLOGY Male Mouth Diseases/*IMMUNOLOGY Mouth Mucosa/IMMUNOLOGY/PATHOLOGY Observer Variation Rats Rats, Inbred BN Rats, Inbred Lew Spleen/CYTOLOGY Support, Non-U.S. Gov't T-Lymphocytes/IMMUNOLOGY/*TRANSPLANTATION Time Factors Tongue/IMMUNOLOGY/PATHOLOGY JOURNAL ARTICLE


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