Akiko Hiroki

Oral involvement in chronic graft-versus-host disease after allogeneic bone marrow transplantation

We examined 37 patients who had undergone an allogeneic bone marrow transplantation and compared their oral findings to their systemic involvement with chronic graft-versus-host disease. Among the clinical signs and symptoms in their oral region, only the presence of oral lichenoid lesions had a statistically significant relationship to the diagnosis of chronic graft-versus-host disease. The histologic findings in the labial salivary glands and buccal mucosa closely reflected the status of chronic graft-versus-host disease. Statistically, the presence of diffuse and periductal lymphocytic infiltration in labial salivary glands, subepithelial lymphocytic infiltration and epithelial changes in buccal mucosa also showed a significant relationship to the diagnosis of chronic graft-versus-host disease. The present study suggests that a systematic oral examination, especially pathologic examination of the labial salivary glands and buccal mucosa, is useful in evaluating the status of chronic graft-versus-host disease.

A comparison of glandular involvement between chronic graft-versus-host disease and Sjögren's syndrome.

Patients with chronic graft-versus-host disease (cGVHD) occasionally suffer from symptoms of xerostomia and xerophthalmia, which are also features of Sjógrens syndrome (SS). To identify differences in the glandular involvement between cGVHD and SS, we measured the proportions of infiltrating lymphocyte subsets and the expression of HLA-DR antigen and cell adhesion molecules in labial salivary glands (LSG). In cGVHD, more than 90% of the infiltrating lymphocytes were T cells with a slight predominance of CD8+ over CD4+ cells. In SS, CD4+ cells were predominant, and B cells accounted for 10-30% of the infiltrating lymphocytes. Ductal epithelial cell associated with lymphocytic infiltration expressed HLA-DR antigen in both cGVHD and SS. In SS alone, HLA-DR antigen expression also occurred without associated lymphocytic infiltration. The expression of adhesion molecules on ductal epithelial cells, especially vascular cell adhesion molecule 1, was more intense in SS than in cGVHD, while that on endothelial cell was similar in cGVHD and SS. These data suggest that the pathogenesis of glandular involvement of cGVHD is different from that of SS.

T-cell receptor Vα and Vβ gene use by infiltrating T cells in labial glands of patients with Sjögren's syndrome

Sjogrens syndrome is an autoimmune disease affecting the exocrine glands; it is thought to result from T-cell-mediated damage. In the labial glands of 20 patients with Sjogrens syndrome, infiltrating T cells were immunohistochemically characterized, and T-cell receptor (TCR) gene expression was examined with a method based on polymerase chain reaction. Most of these lymphocytes expressed CD3, CD4, CD45RO, and TCRαβ, whereas less than 5% of them expressed CD25 and CD69. The TCR Vα and Vβ genes expressed in peripheral blood mononuclear cells were diverse, whereas the TCR Vα and Vβ repertoires in the labial glands were more restricted but were still heterogeneous. The predominantly used Vα and Vβ families in the labial glands, when compared with those in peripheral blood mononuclear cells, were found to vary in individual patients and also to differ from patient to patient. Thus the T-cell population in the labial glands was polyclonal but showed a more restricted pattern than that seen in peripheral blood mononuclear cells.

T cell receptor V&; and V&; gene usage by tumour-infiltrating lymphocytes in oral squamous cell carcinoma

Abstract Oral squamous cell carcinomas (SCC) are often infiltrated by a large number of T lymphocytes. To clarify the nature of the tumour-infiltrating lymphocytes (TIL), we examined T cell receptor (TCR) Vα and Vβ gene usage by TIL and peripheral blood mononuclear cells (PBMC) obtained from 10 patients with oral SCC. We obtained RNA from TIL and PBMC, synthesized complementary DNA, and used the polymerase chain reaction (PCR) method with a panel of primers specific for the V gene segment subfamily (Vα1 – 18/Vβ1 – 20). We thus found that TIL showed more restricted usage of Vβ gene families in contrast to PBMC of the same patients while two unique Vβ gene (Vβ6 and Vβ5.2) segment transcripts were overexpressed in the TIL of more than half of the patients. On the other hand, no major difference was observed in the Vα gene usage between the TIL and PBMC of most patients. To characterize these T cell subpopulations with unique Vβ gene segment transcripts further, we sequenced the complementarity-determining region 3 in Vβ6-Cβ and Vβ5.2-Cβ PCR products derived from TIL and PBMC of two selected patients in each case. Although no usage of the conserved amino acid sequence by TIL was detected, the frequent use of Vβ6/Jβ1.1 in one patient and the Vβ6/Jβ2.7 gene segments in another patient was observed. Regarding the Vβ5.2 transcripts, obtained from the other two patients, no preferential usage of specific Jβ gene segments by TIL was observed. These results suggest that the unique T cell populations are amplified in patients with oral SCC, possibly as a consequence of an in situ immune reaction.

T cell receptor Vα and Vβ gene usage by tumour-infiltrating lymphocytes in oral squamous cell carcinoma

Fig. 1 The expression of T cell receptor (TCR) Va gene transcripts in tumour-infiltrating lymphocytes (TIL) and peripheral blood mononuclear cells (PBMC) from patient 9. Upper section autoradiographs of the polymerase chain reaction (PCR) products for each Va gene family. Va gene transcripts amplified by PCR through 27 cycles were loaded onto 1.8% agarose gel, transferred to a fulter and then hybridized with a 32P-labelled Ca probe, as outlined in Materials and methods.