Summary Autoimmune thyroid diseases are characterized by intrathyroidal infiltration of CD4+ and CD8 + T lymphocytes reactive to self-thyroid antigens. Early studies analysing T cell receptor (TCR) Va gene usage have shown oligoclonal expansion of intrathyroidal T lymphocytes but not peripheral blood T cells. However, TCR Vb diversity of the isolated CD4 + and CD8 + T cell compartments in the peripheral blood has not been characterized fully in these patients. We performed complementarity-determining region 3 (CDR3) spectratyping as well as flow cytometric analysis for the TCR Vb repertoire in peripheral CD4+ and CD8 + T cells from 13 patients with Graves' disease and 17 patients with Hashimoto's thyroiditis. Polyclonal TCR Vb repertoire was demonstrated by flow cytometry in both diseases. In contrast, CDR3 spectratyping showed significantly higher skewing of TCR Vb in peripheral CD8 + T cells but not CD4+ T cells among patients with Hashimoto's thyroiditis compared with healthy adults. We found trends towards a more skewed CDR3 size distribution in those patients having disease longer than 5 years and requiring thyroid hormone replacement. Patients with Graves' disease exhibited no skewing both in CD4 + and CD8 + T cells. These findings indicate that clonal expansion of CD8 + T cells in Hashimoto's thyroiditis can be detected in peripheral blood and may support the role of CD8+ T cells in cell-mediated autoimmune attacks on the thyroid gland in Hashimoto's thyroiditis.

Leukocyte adhesion deficiency type 1 (LAD-1) is an autosomal recessive disorder caused by mutations in the ITGB2 (CD18) gene and characterized by recurrent severe infections, impaired pus formation, and defective wound healing. We describe an unusual case of severe phenotypic LAD-1 presenting with somatic mosaicism. The patient is a compound heterozygote bearing 2 different frameshift mutations that abrogate protein expression. However, CD18 expression was detected in a small proportion of T cells but was undetectable in granulocytes, monocytes, B cells, and natural killer (NK) cells. The T cells were not of maternal origin, lacked the paternal mutation, and showed a selective advantage in vivo.Molecular analysis using sorted CD18 ؉ cells revealed them to be derived from a single CD8 ؉ T cell carrying T-cell receptor VB22. These findings suggest that spontaneous in vivo reversion was responsible for the somatic mosaicism in our patient. (Blood.

Hemophagocytic lymphohistiocytosis (HLH) is a severe and often fatal condition characterized by uncontrolled activation of T cells and macrophages. In Epstein-Barr virus (EBV)-associated HLH (EBV-HLH), the pathogenic roles of ectopic EBV infection in the T-cell population and of clonal proliferation of EBV-infected T cells has been described. However, the immunophenotype of EBV-infected T cells has not been fully characterized. Here we describe a case of EBV-HLH presenting with a massive clonal proliferation of CD8(+) T cells with TCR VB14. Analysis of in situ hybridization for EBV-encoded small RNA1 showed that only CD8(+) T cells harbored EBV in this patient. The EBV-infected TCR VB14(+) CD8(+) T cells exhibited unique immunophenotypic features including lacked CD5 expression and a markedly bright expression of HLA-DR. After initiation of treatment with prednisolone, etoposide, and cyclosporin A, the percentage of infected cells declined progressively in parallel with other serum markers such as ferritin. These findings suggest that lacking expression of CD5 on CD8(+) T cells with specific TCR VB may serve as a useful marker of dysregulated T-cell activation and proliferation in EBV-HLH.

Leukocyte adhesion deficiency type 1 (LAD-1) is an autosomal recessive disorder caused by mutations in the ITGB2 (CD18) gene and characterized by recurrent severe infections, impaired pus formation, and defective wound healing. We describe an unusual case of severe phenotypic LAD-1 presenting with somatic mosaicism. The patient is a compound heterozygote bearing 2 different frameshift mutations that abrogate protein expression. However, CD18 expression was detected in a small proportion of T cells but was undetectable in granulocytes, monocytes, B cells, and natural killer (NK) cells. The T cells were not of maternal origin, lacked the paternal mutation, and showed a selective advantage in vivo. Molecular analysis using sorted CD18+ cells revealed them to be derived from a single CD8+ T cell carrying T-cell receptor VB22. These findings suggest that spontaneous in vivo reversion was responsible for the somatic mosaicism in our patient.

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