scholarly journals Highly functional T-cell receptor repertoires are abundant in stem memory T cells and highly shared among individuals

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Takahiko Miyama ◽  
Takakazu Kawase ◽  
Kazutaka Kitaura ◽  
Ren Chishaki ◽  
Masashi Shibata ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Memory T Cells ◽  
Cell Receptor

scholarly journals P083 Characterisation of T-cell receptor repertoire patterns of circulating a4b7 positive memory T cells in ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S176-S177
Author(s):  
A Gamliel ◽  
L Werner ◽  
N Salamon ◽  
M Pinsker ◽  
B Weiss ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Memory T Cells ◽  
Cell Receptor ◽  
Control Subjects ◽  
Receptor Repertoire ◽  
Negative Memory ◽  
T Cell Receptor Repertoire ◽  
Cell Receptor Repertoire

Abstract Background Memory T cells play an important role in mediating inflammatory responses in IBD. The integrin a4b7 is highly expressed on activated T cells, and is thought to direct homing of lymphocytes to the intestine, following its binding to MADCAM-1 expressed exclusively on intestinal endothelial cells. Since UC is characterised by oligoclonal expansion of specific T-cell clonotypes, we hypothesised that circulating memory T cells with gut-homing potential would exhibit unique T-cell receptor repertoire features. Methods Peripheral blood mononuclear cells were collected from 5 control subjects and 6 pediatric patients with active UC. Following CD3 MACS sorting cells were FACS sorted into a4b7 positive and a4b7 negative CD3+CD45RO+ memory T cells. DNA was Isolated from each subset and subjected to next-generation sequencing of the TCRB. This high-throughput platform employs massive parallel sequencing to process millions of rearranged T-cell receptor (TCR) products simultaneously, and permits an in-depth analysis of individual TCRs at the nucleotide level. Comparisons of different indices of diversity, CDR3 length and clonal biochemical characteristics were performed between a4b7 positive and a4b7 negative populations for each subject, and between controls and UC patients. Results PBMCs were isolated from active UC patients during endoscopic assessment. Four patients had a Mayo endoscopic score of 2, and two patients had a score of 1. Only one patient was treated with an immunosuppressive medication (azathioprine), and five out of six patients were treated with 5ASAs. Percentages of memory T cells (43.8 ± 12.3% vs. 32.2 ± 13.1%, p = 0.17) and a4b7 positive T cells (33.6 ± 15.7% vs. 36.0 ± 17.6%, p = 0.81) were comparable between controls and UC patients. Interestingly, a4b7 positive memory T cells displayed a polyclonal distribution, in both control subjects and in UC patients, without expansion of specific clones. Different indices of diversity, including shanon’s H, clonality index and entropy, were similar among controls and patients, both for a4b7 positive and a4b7 negative populations. Finally, clonal overlap between a4b7 positive and a4b7 negative memory T cells, for each subject was high, ranging between 30–50% for controls and 27–48% for UC patients. Conclusion a4b7 expressing memory T cells exhibited a polyclonal repertoire in both control subjects and patients with active UC, with high rates of overlap with a4b7 negative memory T cells. Our study, along with additional recent reports, challenge the dogma of the importance of a4b7 expression for T-cell migration to the gut, and may suggest that vedolizumab’s suppresses intestinal inflammation by blocking the trafficking of innate immune subsets.

scholarly journals Quantitative Analysis of T-Cell Receptor β Variable-Gene Usage in Cutaneous Late-Phase Reactions: Implications for T-Lymphocyte Recruitment in Cutaneous Inflammation

1999 ◽  
Vol 6 (1) ◽  
pp. 85-88 ◽  
Author(s):  
Stuart R. Lessin ◽  
Bernice M. Benoit ◽  
Guoqing Li ◽  
Ann Moskovitz ◽  
Burton Zweiman
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
T Lymphocyte ◽  
Memory T Cells ◽  
Immunoglobulin E ◽  
Late Phase ◽  
Cell Receptor ◽  
T Cell Subsets ◽  
Variable Gene

ABSTRACT To determine if functionally distinct T-lymphocyte (T cell) subsets accumulate in late-phase immunoglobulin E-mediated reactions (LPR), we quantitatively analyzed the immunophenotype and the T-cell receptor β variable-gene (Vβ) repertoire of T cells in cutaneous LPR. Peripheral blood and skin biopsies were obtained 6 or 24 h after sensitive subjects were challenged with intradermal injections of grass pollen allergen (Ag) and control (C) solution. The frequency of cells expressing CD3, CD4, CD8, CD45RO, and CD25/mm2 was determined by immunohistochemistry in nine subjects. Vβ usage was assessed by reverse transcription-PCR in five of nine subjects. A significantly greater frequency of CD3+ and CD45RO+ (memory) T cells was detected in Ag sites than in C sites at 24 h after challenge but not at 6 h. The frequency of activated (CD25+) and helper (CD4+) T cells appeared to be increased in Ag sites as well, though not significantly. Vβ6 was the most commonly expressed Vβ detected in Ag sites, but it was also detected in accompanying C sites. Vβ2 was the most commonly expressed Vβ detected in C sites. Sequence analysis in one case revealed Vβ expression in a 6-h Ag site to be essentially polyclonal. Our findings suggest that memory T cells with Vβ expression similar to that in normal skin accumulate in developing cutaneous LPR. The limited usage of Vβ suggests a preferential recruitment or retention of reactive T cells from an endogenous subset of skin-homing T cells with its own skewed Vβ repertoire.

scholarly journals Transcriptional programming and T cell receptor repertoires distinguish human lung and lymph node memory T cells

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Nathan Schoettler ◽  
Cara L Hrusch ◽  
Kelly M Blaine ◽  
Anne I Sperling ◽  
Carole Ober
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
T Cell Receptor ◽  
Human Lung ◽  
Memory T Cells ◽  
Cell Receptor ◽  
T Cell Subsets ◽  
Memory T Cell ◽  
Specific Memory

Abstract Antigen-specific memory T cells persist for years after exposure to a pathogen and provide effective recall responses. Many memory T cell subsets have been identified and differ in abundance throughout tissues. This study focused on CD4 and CD8 memory T cells from paired human lung and lung draining lymph node (LDLN) samples and identified substantial differences in the transcriptional landscape of these subsets, including higher expression of an array of innate immune receptors in lung T cells which were further validated by flow cytometry. Using T cell receptor analysis, we determined the clonal overlap between memory T cell subsets within the lung and within the LDLN, and this was greater than the clonal overlap observed between memory T cell subsets compared across tissues. Our results suggest that lung and LDLN memory T cells originate from different precursor pools, recognize distinct antigens and likely have separate roles in immune responses.

scholarly journals Chemokine Receptor Expression Identifies Pre–T Helper (Th)1, Pre–Th2, and Nonpolarized Cells among Human CD4+ Central Memory T Cells

2004 ◽  
Vol 200 (6) ◽  
pp. 725-735 ◽  
Author(s):  
Laura Rivino ◽  
Mara Messi ◽  
David Jarrossay ◽  
Antonio Lanzavecchia ◽  
Federica Sallusto ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Memory T Cells ◽  
Cell Receptor ◽  
Central Memory ◽  
Th2 Cells ◽  
T Helper ◽  
Central Memory T Cells ◽  
Th 1

We previously reported that central–memory T cells (TCM cells), which express lymph node homing receptors CCR7 and CD62L, are largely devoid of effector functions but acquire characteristics of effector–memory T cells (TEM cells) (i.e., CCR7− T helper [Th]1 or Th2 cells) after stimulation with T cell receptor agonists or homeostatic cytokines. Here we show that three chemokine receptors identify functional subsets within the human CD4+ TCM cell pool. TCM cells expressing CXCR3 secreted low amounts of interferon γ, whereas CCR4+ TCM cells produced some interleukin (IL)-4, but not IL-5. In response to IL-7 and IL-15, CXCR3+ TCM and CCR4+ TCM cells invariably generated fully differentiated CCR7− Th1 and Th2 cells, respectively, suggesting that they represent pre-Th1 and pre-Th2 cells. Conversely, CXCR5+ TCM cells lacking CXCR3 and CCR4 remained nonpolarized and retained CCR7 and CD62L expression upon cytokine-driven expansion. Unlike naive cells, all memory subsets had a low T cell receptor rearrangement excision circle content, spontaneously incorporated bromodeoxyuridine ex vivo, and contained cells specific for tetanus toxoid. Conversely, recall responses to cytomegalovirus and vaccinia virus were largely restricted to CXCR3+ TCM and TEM cells. We conclude that antigen-specific memory T cells are distributed between TEM cells and different subsets of TCM cells. Our results also explain how the quality of primary T cell responses could be maintained by TCM cells in the absence of antigen.

scholarly journals Early establishment of diverse T cell receptor profiles for influenza-specific CD8+CD62Lhi memory T cells

2006 ◽  
Vol 103 (24) ◽  
pp. 9184-9189 ◽  
Author(s):  
K. Kedzierska ◽  
V. Venturi ◽  
K. Field ◽  
M. P. Davenport ◽  
S. J. Turner ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Memory T Cells ◽  
Cell Receptor ◽  
Early Establishment

scholarly journals Anergy in Peripheral Memory Cd4+ T Cells Induced by Low Avidity Engagement of T Cell Receptor

2001 ◽  
Vol 194 (6) ◽  
pp. 719-732 ◽  
Author(s):  
Saied Mirshahidi ◽  
Ching-Tai Huang ◽  
Scheherazade Sadegh-Nasseri
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd4 T Cells ◽  
Memory T Cells ◽  
Critical Role ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Memory Cd4 T Cells

Induction of tolerance in self-reactive memory T cells is an important process in the prevention of autoimmune responses against peripheral self-antigens in autoimmune diseases. Although naive T cells can readily be tolerized, memory T cells are less susceptible to tolerance induction. Recently, we demonstrated that low avidity engagement of T cell receptor (TCR) by low densities of agonist peptides induced anergy in T cell clones. Since memory T cells are more responsive to lower antigenic stimulation, we hypothesized that a low avidity TCR engagement may induce tolerance in memory T cells. We have explored two antigenic systems in two transgenic mouse models, and have tracked specific T cells that are primed and show memory phenotype. We demonstrate that memory CD4+ T cells can be rendered anergic by presentation of low densities of agonist peptide–major histocompatibility complex complexes in vivo. We rule out other commonly accepted mechanisms for induction of T cell tolerance in vivo, such as deletion, ignorance, or immunosuppression. Anergy is the most likely mechanism because addition of interleukin 2–reversed anergy in specific T cells. Moreover, cytotoxic T lymphocyte antigen (CTLA)-4 plays a critical role in the induction of anergy because we observed that there was increased surface expression of CTLA-4 on anergized T cells, and that injection of anti–CTLA-4 blocking antibody restored anergy in vivo.

scholarly journals Circulating α4β7+ Memory T Cells in Pediatric IBD Patients Express a Polyclonal T Cell Receptor Repertoire

2020 ◽  
Vol Volume 13 ◽  
pp. 439-447
Author(s):  
Adir Gamliel ◽  
Lael Werner ◽  
Marina Pinsker ◽  
Naomi Salamon ◽  
Batia Weiss ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Memory T Cells ◽  
Cell Receptor ◽  
Receptor Repertoire ◽  
T Cell Receptor Repertoire ◽  
Cell Receptor Repertoire ◽  
Pediatric Ibd

scholarly journals Balancing Inflammation and Central Nervous System Homeostasis: T Cell Receptor Signaling in Antiviral Brain TRM Formation and Function

2021 ◽  
Vol 11 ◽  
Author(s):  
Colleen S. Netherby-Winslow ◽  
Katelyn N. Ayers ◽  
Aron E. Lukacher
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Memory T Cells ◽  
Infectious Agent ◽  
Cell Receptor ◽  
Effector Memory ◽  
Tcr Signaling ◽  
And Function ◽  
Barrier Tissues

Tissue-resident memory (TRM) CD8 T cells provide early frontline defense against regional pathogen reencounter. CD8 TRM are predominantly parked in nonlymphoid tissues and do not circulate. In addition to this anatomic difference, TRM are transcriptionally and phenotypically distinct from central-memory T cells (TCM) and effector-memory T cells (TEM). Moreover, TRM differ phenotypically, functionally, and transcriptionally across barrier tissues (e.g., gastrointestinal tract, respiratory tract, urogenital tract, and skin) and in non-barrier organs (e.g., brain, liver, kidney). In the brain, TRM are governed by a contextual milieu that balances TRM activation and preservation of essential post-mitotic neurons. Factors contributing to the development and maintenance of brain TRM, of which T cell receptor (TCR) signal strength and duration is a central determinant, vary depending on the infectious agent and modulation of TCR signaling by inhibitory markers that quell potentially pathogenic inflammation. This review will explore our current understanding of the context-dependent factors that drive the acquisition of brain (b)TRM phenotype and function, and discuss the contribution of TRM to promoting protective immune responses in situ while maintaining tissue homeostasis.

scholarly journals Characteristics of T-cell receptor repertoire of stem cell-like memory CD4+ T cells

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11987
Author(s):  
Shiyu Wang ◽  
Longlong Wang ◽  
Yang Liu ◽  
Yonggang Zhu ◽  
Ya Liu
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
T Cell Receptor ◽  
Memory T Cells ◽  
Human Subjects ◽  
Length Distribution ◽  
Cell Receptor ◽  
Receptor Repertoire ◽  
Cdr3 Region

Stem cell-like memory T cells (Tscm) combine phenotypes of naïve and memory. However, it remains unclear how T cell receptor (TCR) characteristics contribute to heterogeneity in Tscm and other memory T cells. We compared the TCR-beta (TRB) repertoire characteristics of CD4+ Tscm with those of naïve and other CD4+ memory (Tm) in 16 human subjects. Compared with Tm, Tscm had an increased diversity across all stretches of TRB repertoire structure, a skewed gene usage, and a shorter length distribution of CDR3 region. These distinctions between Tscm and Tm were enlarged in top1000 abundant clonotypes. Furthermore, top1000 clonotypes in Tscm were more public than those in Tm and grouped in more clusters, implying more epitope types recognized by top1000 clonotypes in Tscm. Importantly, self-reactive clonotypes were public and enriched in Tscm rather than Tm, of type one diabetes patients. Therefore, this study highlights the unique features of Tscm different from those of other memory subsets and provides clues to understand the physiological and pathological functions of Tscm.

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