Case 1: Diversity index of mucosal resident T lymphocyte repertoire predicts clinical prognosis in gastric cancer
Gastric cancer is one of the most common malignant cancer in China. TNM staging is widely used to assess postoperative outcomes and adjuvant therapy, but it is not accurate enough. In a retrospective study of 28 primary gastric cancer patients in Southwest Hospital of Third Military Medical University, we sequenced TCR repertoire within patient's tumor, adjacent mucosa and peripheral blood. We established the diversity index of mucosal resident TCR repertoire as an important indicator for prognosis of gastric cancer. Figure C shows that NSDE of mucosal TCR repertoire is the most significant marker to predict prognosis.
Case 2: Association of CD8(+) T lymphocyte repertoire spreading with the severity of DRESS syndrome
Drug hypersensitivity syndrome (DRESS) is a rare but life-threatening syndrome, which was characterized by a long latency period and a prolonged disease course with frequent relapses despite the discontinuation of the culprit drug. However, the characteristics of the TCR repertoire and the clinical significance of repertoire reformation throughout the course of DRESS are unknown. We isolated CD4- and CD8-T cells from peripheral blood of 8 DRESS patients at 10-day intervals and, sequenced CDR3-regions of the TCRB chain by high-throughput sequencing to analyze the dynamic reformation in the T-cell repertoire hierarchy. We established the positive correlation of fluctuant CD8(+) T-cell repertoires and severity of DRESS syndrome.
Case 3: T cell receptor sequencing revealed the natural selection of long-lived T cell clones under healthy conditions
Most naïve T cells are short-lived due to lack of antigen encounter, whereas antigen-experienced T cells may survive and persist as long-lived clones. Thus far, little is known about the homeostasis, antigenic specificity, and clonal diversity of long-lived T-cell clones in peripheral lymphoid organs under healthy living conditions. In collaboration with the Department of Immunology, Duke University School of Medicine, we designed a lineage-tracing method to label a wave of T cells produced in the thymus of young mice. Through T-cell receptor repertoire analysis, we revealed that the lineage-tracked CD4 memory-like T cells and T regulatory cells exhibited age-dependent enrichment of shared clonotypes.
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