scholarly journals Brain Citrullination Patterns and T Cell Reactivity of Cerebrospinal Fluid-Derived CD4+ T Cells in Multiple Sclerosis

2019 ◽  
Vol 10 ◽  
Author(s):  
Wolfgang Faigle ◽  
Carolina Cruciani ◽  
Witold Wolski ◽  
Bernd Roschitzki ◽  
Marco Puthenparampil ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Cerebrospinal Fluid ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cell Reactivity ◽  
T Cell Reactivity

Positive conversion of negative signaling of CTLA4 potentiates antitumor efficacy of adoptive T-cell therapy in murine tumor models

Blood ◽  
2012 ◽  
Vol 119 (24) ◽  
pp. 5678-5687 ◽  
Author(s):  
Jae Hun Shin ◽  
Hyung Bae Park ◽  
Yu Mi Oh ◽  
Dong Pyo Lim ◽  
Ji Eun Lee ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Tumor Antigen ◽  
Cd4 T Cells ◽  
Antitumor Effect ◽  
Gene Modification ◽  
Cell Reactivity ◽  
Murine Tumor ◽  
T Cell Reactivity

Abstract Cytotoxic T lymphocyte–associated antigen 4 (CTLA4) has been known to be a strong tolerance-inducing inhibitory receptor on T-cell surface. Systemic blocking of CTLA4 function with blocking antibodies has been regarded as an attractive strategy to enhance antitumor immunity. However, this strategy accompanies systemic autoimmune side effects that are sometimes problematic. Therefore, we developed a novel CTLA4 mutant that could be expressed in tumor antigen-specific T cells to enhance antitumor effect without systemic autoimmunity. This mutant, named CTLA4-CD28 chimera, consists of extracellular and transmembrane domains of CTLA4, linked with cytoplasmic CD28 domain. Overexpression of CTLA4-CD28 chimera in T cells delivered stimulatory signals rather than inhibitory signals of CTLA4 and significantly enhanced T-cell reactivity. Although this effect was observed in both CD4 and CD8 T cells, the effect on CD4 T cells was predominant. CTLA4-CD28 chimera gene modification of CD4 T cells significantly enhanced antitumor effect of unmodified CD8 T cells. Nonetheless, the gene modification of CD8 T cells along with CD4 T cells further maximized antitumor effect of T cells in 2 different murine tumor models. Thus, CTLA4-CD28 chimera gene modification of both tumor antigen-specific CD4 and CD8 T cells would be an ideal way of modulating CTLA4 function to enhance tumor-specific T-cell reactivity.

scholarly journals The MRC OX-22- CD4+ T cells that help B cells in secondary immune responses derive from naive precursors with the MRC OX-22+ CD4+ phenotype.

1989 ◽  
Vol 169 (3) ◽  
pp. 653-662 ◽  
Author(s):  
F Powrie ◽  
D Mason
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Cd4 T Cells ◽  
Antibody Responses ◽  
Cell Reactivity ◽  
Helper Activity ◽  
T Cell Reactivity ◽  
Paper Address

CD4+ T cells in the rat can be divided into two nonoverlapping subsets by their reactivity with the mAb MRC OX-22, which binds some of the high molecular weight forms of the CD45 antigen. The lineage relationship between subsets of CD4+ T cells expression different forms of CD45 has been a controversial issue for some time. Experiments described in this paper address this question using in vivo assays of T cell reactivity. Analysis of primary antibody responses in vivo show that it is MRC OX-22+ CD4+ T cells that are active in these assays, whereas antigen-primed T cells that provide helper activity for secondary antibody responses in vivo have the MRC OX-22- CD4+ phenotype. It is demonstrated that these memory T cells derive from MRC OX-22+ CD4+ T cell precursors and not from a putative separate lineage. It is concluded that with respect to the provision of help for B cells, MRC OX-22+ CD4+ T cells are precursors of memory cells with the phenotype MRC OX-22- CD4+.

scholarly journals Cytomegalovirus-specific T-cell reactivity in biliary atresia at the time of diagnosis is associated with deficits in regulatory T cells

Hepatology ◽  
2012 ◽  
Vol 55 (4) ◽  
pp. 1130-1138 ◽  
Author(s):  
Stephen M. Brindley ◽  
Allison M. Lanham ◽  
Frederick M. Karrer ◽  
Rebecca M. Tucker ◽  
Andrew P. Fontenot ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Biliary Atresia ◽  
Cell Reactivity ◽  
T Cell Reactivity

scholarly journals Relationship between Multiple Sclerosis-Associated IL2RA Risk Allele Variants and Circulating T Cell Phenotypes in Healthy Genotype-Selected Controls

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 634 ◽  
Author(s):  
Sophie Buhelt ◽  
Helle Bach Søndergaard ◽  
Annette Oturai ◽  
Henrik Ullum ◽  
Marina Rode von Essen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Interleukin 2 ◽  
T Cell Subsets ◽  
Multiparameter Flow Cytometry ◽  
Risk Genotype ◽  
Increased Risk ◽  
New Findings

Single nucleotide polymorphisms (SNPs) in or near the IL2RA gene, that encodes the interleukin-2 (IL-2) receptor α (CD25), are associated with increased risk of immune-mediated diseases including multiple sclerosis (MS). We investigated how the MS-associated IL2RA SNPs rs2104286 and rs11256593 are associated with CD25 expression on T cells ex vivo by multiparameter flow cytometry in paired genotype-selected healthy controls. We observed that MS-associated IL2RA SNPs rs2104286 and rs11256593 are associated with expression of CD25 in CD4+ but not CD8+ T cells. In CD4+ T cells, carriers of the risk genotype had a reduced frequency of CD25+ TFH1 cells (p = 0.001) and an increased frequency of CD25+ recent thymic emigrant cells (p = 0.006). Furthermore, carriers of the risk genotype had a reduced surface expression of CD25 in post-thymic expanded CD4+ T cells (CD31−CD45RA+), CD39+ TReg cells and in several non-follicular memory subsets. Our study found novel associations of MS-associated IL2RA SNPs on expression of CD25 in CD4+ T cell subsets. Insight into the associations of MS-associated IL2RA SNPs, as these new findings provide, offers a better understanding of CD25 variation in the immune system and can lead to new insights into how MS-associated SNPs contribute to development of MS.

scholarly journals HCoV- and SARS-CoV-2 Cross-Reactive T Cells in CVID Patients

2020 ◽  
Vol 11 ◽  
Author(s):  
Sophie Steiner ◽  
Franziska Sotzny ◽  
Sandra Bauer ◽  
Il-Kang Na ◽  
Michael Schmueck-Henneresse ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
T Cell Responses ◽  
Cross Reactivity ◽  
T Cell Immunity ◽  
Cell Reactivity ◽  
Cd8 Cells ◽  
Cell Responses ◽  
Cell Immunity

The inability of patients with CVID to mount specific antibody responses to pathogens has raised concerns on the risk and severity of SARS-CoV-2 infection, but there might be a role for protective T cells in these patients. SARS-CoV-2 reactive T cells have been reported for SARS-CoV-2 unexposed healthy individuals. Until now, there is no data on T cell immunity to SARS-CoV-2 infection in CVID. This study aimed to evaluate reactive T cells to human endemic corona viruses (HCoV) and to study pre-existing SARS-CoV-2 reactive T cells in unexposed CVID patients. We evaluated SARS-CoV-2- and HCoV-229E and –OC43 reactive T cells in response to seven peptide pools, including spike and nucleocapsid (NCAP) proteins, in 11 unexposed CVID, 12 unexposed and 11 post COVID-19 healthy controls (HC). We further characterized reactive T cells by IFNγ, TNFα and IL-2 profiles. SARS-CoV-2 spike-reactive CD4+ T cells were detected in 7 of 11 unexposed CVID patients, albeit with fewer multifunctional (IFNγ/TNFα/IL-2) cells than unexposed HC. CVID patients had no SARS-CoV-2 NCAP reactive CD4+ T cells and less reactive CD8+ cells compared to unexposed HC. We observed a correlation between T cell reactivity against spike of SARS-CoV-2 and HCoVs in unexposed, but not post COVID-19 HC, suggesting cross-reactivity. T cell responses in post COVID-19 HC could be distinguished from unexposed HC by higher frequencies of triple-positive NCAP reactive CD4+ T cells. Taken together, SARS-CoV-2 reactive T cells are detectable in unexposed CVID patients albeit with lower recognition frequencies and polyfunctional potential. Frequencies of triple-functional reactive CD4+ cells might provide a marker to distinguish HCoV cross-reactive from SARS-CoV-2 specific T cell responses. Our data provides evidence, that anti-viral T cell immunity is not relevantly impaired in most CVID patients.

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