scholarly journals Distorted TCR repertoires define multisystem inflammatory syndrome in children

2021 ◽  
Author(s):  
Amna Malik ◽  
Eszter N. Tóth ◽  
Michelle S. Teng ◽  
Jacob Hurst ◽  
Eleanor Watt ◽  
...  
Keyword(s):  
T Cell ◽  
Severe Acute Respiratory Syndrome ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
High Confidence ◽  
T Cell Clones ◽  
Severity Of Disease ◽  
Cell Clones ◽  
Inflammatory Syndrome ◽  
Independent Expansion

While the majority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) display mild or no symptoms, rare individuals develop severe disease presenting with multisystem inflammatory syndrome (MIS-C). The reason for variable clinical manifestations is not understood. Here, we carried out TCR sequencing and conducted comparative analyses of TCR repertoires between children with severe (n=12) or mild (n=8) COVID-19. We compared these repertoires with unexposed individuals (samples collected pre-COVID-19 pandemic: n=8) and with the Adaptive Biotechnologies MIRA dataset, which includes over 135,000 high-confidence SARS-CoV-2-specific TCRs. We show that the repertoires of severely ill children are characterised by the expansion of TRBV11-2 chains with high junctional and CDR3 diversity. Moreover, the CDR3 sequences of TRBV11-2 clones shift away from SARS-CoV-2 specific T cell clones, resulting in distorted TCR repertoires. In conclusion, our study reports that CDR3-independent expansion of TRBV11-2+ cells, lacking SARS-CoV-2 specificity, defines severity of disease in children.

scholarly journals Differential Functional Avidity of Dengue Virus-Specific T-Cell Clones for Variant Peptides Representing Heterologous and Previously Encountered Serotypes

2007 ◽  
Vol 81 (18) ◽  
pp. 10081-10091 ◽  
Author(s):  
Allison Imrie ◽  
Janet Meeks ◽  
Alexandra Gurary ◽  
Munkhzul Sukhbataar ◽  
Paul Kitsutani ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Dengue Virus ◽  
Severe Disease ◽  
T Cell Clones ◽  
Cell Responses ◽  
Cell Clones ◽  
Tnf Α ◽  
Dengue Virus Serotypes ◽  
Ifn Γ

ABSTRACT Proinflammatory cytokines secreted by memory CD8+ and CD4+ T cells are thought to play a direct role in the pathogenesis of dengue virus infection by increasing vascular permeability and thereby inducing the pathophysiologic events associated with dengue hemorrhagic fever and dengue shock syndrome. Severe disease is frequently observed in the setting of secondary infection with heterologous dengue virus serotypes, suggesting a role for cross-reactive memory T cells in the immunopathogenesis of severe disease. We used a large panel of well-characterized dengue virus-specific CD8+ T-cell clones isolated from Pacific Islanders previously infected with dengue virus 1 to examine effector memory function, focusing on a novel dominant HLA-B*5502-restricted NS5329-337 epitope, and assessed T-cell responses to stimulation with variant peptides representing heterologous serotypes. Variant peptides were differentially recognized by dengue virus 1-specific effector CD8+ cytotoxic T lymphocytes (CTL) in a heterogeneous and clone-specific manner, in which cytolytic function and cytokine secretion could be enhanced, diminished, or abrogated compared with cognate peptide stimulation. Dengue virus-specific CTL stimulated with cognate and variant peptides demonstrated a cytokine response hierarchy of gamma IFN (IFN-γ) > tumor necrosis factor alpha (TNF-α) > interleukin-2 (IL-2), and a subset of clones also produced IL-4 and IL-6. Individual clones demonstrated greater avidity for variant peptides representing heterologous serotypes, including serotypes previously encountered by the subject, and IFN-γ and TNF-α secretion was enhanced by stimulation with these heterologous peptides. Altered antiviral T-cell responses in response to stimulation with heterologous dengue virus serotypes have implications for control of virus replication and for disease pathogenesis.

Human Heart–Infiltrating T-Cell Clones From Rheumatic Heart Disease Patients Recognize Both Streptococcal and Cardiac Proteins

Circulation ◽  
1995 ◽  
Vol 92 (3) ◽  
pp. 415-420 ◽  
Author(s):  
L. Guilherme ◽  
E. Cunha-Neto ◽  
V. Coelho ◽  
R. Snitcowsky ◽  
P. M. A. Pomerantzeff ◽  
...  
Keyword(s):  
Heart Disease ◽  
T Cell ◽  
Rheumatic Heart Disease ◽  
Human Heart ◽  
T Cell Clones ◽  
Cell Clones ◽  
Rheumatic Heart

Bacteria-specific CD4+ T-cell clones induce colitis in helicobacter hepaticus-infected T-cell-deficient RAG-2 KO mice

2001 ◽  
Vol 120 (5) ◽  
pp. A519-A520
Author(s):  
Marika C. Kullberg ◽  
Dragana Jankovic ◽  
Patricia Caspar ◽  
Peter L. Gorelick ◽  
Allen Cheever ◽  
...  
Keyword(s):  
T Cell ◽  
Cd4 T Cell ◽  
Helicobacter Hepaticus ◽  
T Cell Clones ◽  
Cell Clones

Development of Lung Eosinophilic Inflammation by the Infusion of IL-5-Producing T Cell Clones

1997 ◽  
Vol 114 (1) ◽  
pp. 10-13 ◽  
Author(s):  
Osamu Kaminuma ◽  
Akio Mori ◽  
Matsunobu Suko ◽  
Hideo Kikkawa ◽  
Kazuaki Naito ◽  
...  
Keyword(s):  
T Cell ◽  
Eosinophilic Inflammation ◽  
T Cell Clones ◽  
Cell Clones

scholarly journals Self-sparing of long-term in vitro-cloned or uncloned cytotoxic T lymphocytes.

1986 ◽  
Vol 164 (3) ◽  
pp. 962-967 ◽  
Author(s):  
M F Luciani ◽  
J F Brunet ◽  
M Suzan ◽  
F Denizot ◽  
P Golstein
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Cytotoxic T Cell ◽  
Cell Populations ◽  
Con A ◽  
T Cell Clones ◽  
Cell Clones

At least some long-term in vitro-cultured cytotoxic T cell clones and uncloned cell populations are able, in the presence of Con A, to lyse other cells, to be lysed by other cells, but not to lyse themselves. This as-yet-unexplained result may have implications as to the mechanism of T cell-mediated cytotoxicity.

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