Clonal Biases of Peripheral CD8 T Cell Repertoire Directly Reflect Local Inflammation in Polymyositis

Nishio, Juntaro; Suzuki, Mihoko; Miyasaka, Nobuyuki; Kohsaka, Hitoshi

doi:10.4049/jimmunol.167.7.4051

Cited by 59 publications

(47 citation statements)

References 51 publications

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“…T cells are selectively activated and undergoing a massive expansion via specific recognition of tumor neoantigens. T cells repertoires have been identified to coevolve with the spectrum of neoantigens over time, which result in a characteristic manifestation of T cells repertoire specific for malignant tumor in lesion 11, 12…”

Section: Introductionmentioning

confidence: 99%

T cell receptor repertoire profiling predicts the prognosis of HBV‐associated hepatocellular carcinoma

et al. 2018

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Tumor‐infiltrating T cell repertoire has been demonstrated to be closely associated with anti‐tumor immune response. However, the relationship between T cell repertoire in tumor tissue and prognosis has never been reported in Hepatocellular carcinoma (HCC). We performed the high‐throughput T cell receptor (TCR) sequencing to systematically characterize the infiltrating T cell repertoires of tumor and matched adjacent normal tissues from 23 HBV‐associated HCC patients. Significant differences on usage frequencies of some Vβ, Jβ, and Vβ‐Jβ paired genes have been found between the 2 groups of tissue samples, but no significant difference of TCR repertoire diversity could be found. Interestingly, the similarity of TCR repertoires between paired samples or the TNM stage alone could not be helpful to evaluate the prognosis of patients very well, but their combination could serve as an efficient prognostic indicator that the patients with early stage and high similarity showed a better prognosis. This is the first attempt to assess the potential value of TCR repertoire in HCC prognosis, and our findings could serve as a complement for the characterization of TCR repertoire in HCC.

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Section: Introductionmentioning

confidence: 99%

T cell receptor repertoire profiling predicts the prognosis of HBV‐associated hepatocellular carcinoma

et al. 2018

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“…The TCR repertoire in myositis patients has been investigated in a few studies using different methods, such as polymerase chain reaction (PCR), immunohistochemistry, TCR complementarity-determining region 3 (CDR3) length analysis, and flow cytometry, mainly on T cells from muscle tissue, and in some studies, a comparison with the TCR profile in blood was performed (9)(10)(11)(12)(13). A few studies have demonstrated a restricted TCR repertoire in muscle tissue from patients with PM, but without a consistent pattern of TCR V ␤ (BV) gene usage (9,10).…”

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confidence: 99%

Restricted T cell receptor BV gene usage in the lungs and muscles of patients with idiopathic inflammatory myopathies

Englund¹,

Wahlström²,

Fathi³

et al. 2007

Arthritis & Rheumatism

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Objective. To investigate T cell receptor (TCR) expression in 3 different compartments that could be involved in patients with myositis: muscle, lung, and peripheral blood.Methods. Nine patients with polymyositis (PM), dermatomyositis, or inclusion body myositis underwent bronchoscopy and bronchoalveolar lavage (BAL) as well as muscle biopsy and blood sampling. A panel of 19 monoclonal antibodies specific for TCR V ␤ (BV) and V ␣ (AV) were used to characterize the TCR profile in CD4؉ and CD8؉ T cell populations in BAL fluid and peripheral blood by flow cytometry. Muscle biopsy tissues were analyzed by immunohistochemistry. Patients were also typed for HLA-DRB1 and DRB3 alleles.Results. A total of 17 T cell expansions were detected in BAL fluid, 6 in the CD4؉ T cell population and 11 in the CD8؉ T cell population. Four T cell expansions were detected in peripheral blood. A selective TCR V usage was found in muscle. Two PM patients, both of whom had BAL fluid BV3؉ T cell expansions in the CD4 population and in whom BV3 was also a prominent TCR V segment in muscle tissue, shared the HLA-DRB1*03 allele. These 2 patients were the only ones who were positive for anti-Jo-1 antibody.Conclusion. We found a restricted accumulation of T lymphocytes expressing selected TCR V-gene segments in the target organ compartments (i.e., lung and muscle). The occurrence of shared TCR gene segment usage in muscle and lungs could suggest common target antigens in these organs.

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“…Most recently, CDR3 spectratyping has been applied to blood and muscle samples from patients with myositis (37,38). These studies revealed remarkable expansions of CD8ϩ T cells in PM but not dermatomyositis patients (38).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies of the TCR repertoire demonstrated clonally expanded T cell populations in muscle of patients with PM (24,(34)(35)(36)(37)(38). Most recently, CDR3 spectratyping has been applied to blood and muscle samples from patients with myositis (37,38).…”

Section: Discussionmentioning

confidence: 99%

Clonal tracking of autoaggressive T cells in polymyositis by combining laser microdissection, single-cell PCR, and CDR3-spectratype analysis

Hofbauer

Wiesener

Babbe

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

103

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Clonal expansions of CD8؉ T cells have been identified in muscle and blood of polymyositis patients by PCR techniques, including T cell receptor (TCR) complementarity-determining region (CDR)3 length analysis (spectratyping).To examine a possible pathogenic role of these clonally expanded T cells, we combined CDR3 spectratyping with laser microdissection and single-cell PCR of individual myocytotoxic T cells that contact, invade, and destroy a skeletal muscle fiber. First, we screened cDNA from muscle biopsy specimens by CDR3 spectratyping for expanded TCR ␤ chain variable region (BV) sequences. To pinpoint the corresponding T cells in tissue, we stained cryostat sections with appropriate anti-TCR BV mAbs, isolated single BV؉ T cells that directly contacted or invaded a muscle fiber by laser-assisted microdissection, and amplified their TCR BV chain sequences from rearranged genomic DNA. In this way, we could relate the oligoclonal peaks identified by CDR3-spectratype screening to morphologically characterized microdissected T cells. In one patient, a large fraction of the microdissected T cells carried a common TCR-BV amino acid CDR3 motif and conservative nucleotide exchanges in the CDR3 region, suggesting an antigen-driven response. In several cases, we tracked these T cell clones for several years in CD8؉ (but not CD4؉) blood lymphocytes and in two patients also in consecutive muscle biopsy specimens. During immunosuppressive therapy, oligoclonal CDR3-spectratype patterns tended to revert to more polyclonal Gaussian distribution-like patterns. Our findings demonstrate that CDR3 spectratyping and single-cell analysis can be combined to identify and track autoaggressive T cell clones in blood and target tissue. This approach should be applicable to other inflammatory and autoimmune disorders.

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Clonal Biases of Peripheral CD8 T Cell Repertoire Directly Reflect Local Inflammation in Polymyositis

Cited by 59 publications

References 51 publications

T cell receptor repertoire profiling predicts the prognosis of HBV‐associated hepatocellular carcinoma

T cell receptor repertoire profiling predicts the prognosis of HBV‐associated hepatocellular carcinoma

Restricted T cell receptor BV gene usage in the lungs and muscles of patients with idiopathic inflammatory myopathies

Clonal tracking of autoaggressive T cells in polymyositis by combining laser microdissection, single-cell PCR, and CDR3-spectratype analysis

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