scholarly journals Whole blood-based measurement of SARS-CoV-2-specific T cell responses reveals asymptomatic infection and vaccine efficacy in healthy subjects and patients with solid organ cancers

2021 ◽  
Author(s):  
Martin J Scurr ◽  
Wioleta M Zelek ◽  
George Lippiatt ◽  
Michelle S Somerville ◽  
Stephanie E A Burnell ◽  
...  
Keyword(s):  
T Cell ◽  
Cancer Patients ◽  
Whole Blood ◽  
Vaccine Efficacy ◽  
T Cell Responses ◽  
Exact Nature ◽  
Solid Organ ◽  
Cell Responses ◽  
Healthy Donors ◽  
Ifn Γ

Accurate assessment of SARS-CoV-2 immunity in the population is critical to evaluating vaccine efficacy and devising public health policies. Whilst the exact nature of effective immunity remains incompletely defined, SARS-CoV-2-specific T cell responses are a critical feature of the immune response that will likely form a key correlate of protection against COVID-19. Here, we developed and optimised a high-throughput whole blood-based assay to determine the T cell response associated with prior SARS-CoV-2 infection and/or vaccination amongst 156 healthy donors and 67 cancer patients. Following overnight in vitro stimulation with SARS-CoV-2-specific peptides, blood plasma samples were harvested and analysed for Th1-type effector cytokines (IFN-γ and IL-2). Amongst healthy donors, highly significant differential IFN-γ+/IL-2+ SARS-CoV-2-specific T cell responses were seen amongst vaccinated or previously infected COVID-19-positive individuals in comparison to unknown/naïve individuals (P < 0.0001). IL-2 production from T cells in response to SARS-CoV-2 derived antigens was a highly predictive diagnostic assay (P < 0.0001; 96.0% sensitivity, 93.9% specificity); measurement of IFN-γ+ SARS-CoV-2 specific T cell responses was equally effective at identifying asymptomatic (antibody and T cell positive) participants. A single dose of COVID-19 vaccine induced IFN-γ and/or IL-2 SARS-CoV-2-specific T cell responses in 28/29 (96.6%) of healthy donors, reducing significantly to 27/56 (48.2%) when measured in cancer patients (P = 0.0003). Overall, this cost-effective standardisable test ensures accurate and comparable assessments of SARS-CoV-2-specific T cell responses amenable to widespread population immunity testing.

scholarly journals Human kallikrein 4 signal peptide induces cytotoxic T cell responses in healthy donors and prostate cancer patients

2011 ◽  
Vol 61 (2) ◽  
pp. 169-179 ◽  
Author(s):  
Ray Wilkinson ◽  
Katherine Woods ◽  
Rachael D’Rozario ◽  
Rebecca Prue ◽  
Frank Vari ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cell ◽  
Cancer Patients ◽  
Signal Peptide ◽  
T Cell Responses ◽  
Cytotoxic T Cell ◽  
Cell Responses ◽  
Healthy Donors ◽  
Kallikrein 4 ◽  
Cytotoxic T Cell Responses

scholarly journals Melioidosis Patient Survival Correlates With Strong IFN-γ Secreting T Cell Responses Against Hcp1 and TssM

2021 ◽  
Vol 12 ◽  
Author(s):  
Sineenart Sengyee ◽  
Atchara Yarasai ◽  
Rachan Janon ◽  
Chumpol Morakot ◽  
Orawan Ottiwet ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Clinical Manifestations ◽  
T Cell Responses ◽  
Peptide Pool ◽  
Humoral Immune ◽  
Cell Responses ◽  
Humoral Immune Responses ◽  
Healthy Donors ◽  
Ifn Γ

Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is a serious infectious disease with diverse clinical manifestations. The morbidity and mortality of melioidosis is high in Southeast Asia and no licensed vaccines currently exist. This study was aimed at evaluating human cellular and humoral immune responses in Thai adults against four melioidosis vaccine candidate antigens. Blood samples from 91 melioidosis patients and 100 healthy donors from northeast Thailand were examined for immune responses against B. pseudomallei Hcp1, AhpC, TssM and LolC using a variety of cellular and humoral immune assays including IFN-γ ELISpot assays, flow cytometry and ELISA. PHA and a CPI peptide pool were also used as control stimuli in the ELISpot assays. Hcp1 and TssM stimulated strong IFN-γ secreting T cell responses in acute melioidosis patients which correlated with survival. High IFN-γ secreting CD4+ T cell responses were observed during acute melioidosis. Interestingly, while T cell responses of melioidosis patients against the CPI peptide pool were low at the time of enrollment, the levels increased to the same as in healthy donors by day 28. Although high IgG levels against Hcp1 and AhpC were detected in acute melioidosis patients, no significant differences between survivors and non-survivors were observed. Collectively, these studies help to further our understanding of immunity against disease following natural exposure of humans to B. pseudomallei as well as provide important insights for the selection of candidate antigens for use in the development of safe and effective melioidosis subunit vaccines.

A clinical grade poly I:C-analogue (Ampligen®) promotes optimal DC maturation and Th1-type T cell responses of healthy donors and cancer patients in vitro

Vaccine ◽  
2009 ◽  
Vol 27 (1) ◽  
pp. 107-115 ◽  
Author(s):  
H. Navabi ◽  
B. Jasani ◽  
A. Reece ◽  
A. Clayton ◽  
Z. Tabi ◽  
...  
Keyword(s):  
T Cell ◽  
Cancer Patients ◽  
T Cell Responses ◽  
Poly I:C ◽  
Clinical Grade ◽  
Cell Responses ◽  
Healthy Donors ◽  
Dc Maturation

scholarly journals Split T Cell Tolerance against a Self/Tumor Antigen: Spontaneous CD4+ but Not CD8+ T Cell Responses against p53 in Cancer Patients and Healthy Donors

PLoS ONE ◽  
2011 ◽  
Vol 6 (8) ◽  
pp. e23651 ◽  
Author(s):  
Takemasa Tsuji ◽  
Junko Matsuzaki ◽  
Erika Ritter ◽  
Anthony Miliotto ◽  
Gerd Ritter ◽  
...  
Keyword(s):  
T Cell ◽  
Cancer Patients ◽  
Tumor Antigen ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
Cell Responses ◽  
Healthy Donors

Analysis of PSA-Specific T-Cell Responses of Prostate Cancer Patients Given a PSA-Based Vaccine on a Clinical Trial

2003 ◽  
Author(s):  
James Gulley ◽  
William Dahut ◽  
Philip M. Arlen ◽  
Kwong Tsang ◽  
Jeffrey Schlom
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
T Cell ◽  
Cancer Patients ◽  
T Cell Responses ◽  
Cell Responses

scholarly journals Whole blood interleukin‐2 release test to detect and characterise rare circulating gluten‐specific t cell responses in coeliac disease

2021 ◽  
Author(s):  
Robert P Anderson ◽  
Gautam Goel ◽  
Melinda Y. Hardy ◽  
Amy K. Russell ◽  
Suyue Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Coeliac Disease ◽  
Whole Blood ◽  
Interleukin 2 ◽  
T Cell Responses ◽  
Cell Responses ◽  
Release Test

scholarly journals Batf3-Dependent Dendritic Cells Promote Optimal CD8 T Cell Responses against Respiratory Poxvirus Infection

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Pritesh Desai ◽  
Vikas Tahiliani ◽  
Georges Abboud ◽  
Jessica Stanfield ◽  
Shahram Salek-Ardakani
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Vaccinia Virus ◽  
Respiratory Infection ◽  
Host Resistance ◽  
T Cell Responses ◽  
Cell Responses ◽  
Ifn Γ ◽  
The Impact

ABSTRACTRespiratory infection with vaccinia virus (VacV) elicits robust CD8+T cell responses that play an important role in host resistance. In the lung, VacV encounters multiple tissue-resident antigen-presenting cell (APC) populations, but which cell plays a dominant role in priming of virus-specific CD8+effector T cell responses remains poorly defined. We used Batf3−/−mice to investigate the impact of CD103+and CD8α+dendritic cell (DC) deficiency on anti-VacV CD8+T cell responses. We found that Batf3−/−mice were more susceptible to VacV infection, exhibiting profound weight loss, which correlated with impaired accumulation of gamma interferon (IFN-γ)-producing CD8+T cells in the lungs. This was largely due to defective priming since early in the response, antigen-specific CD8+T cells in the draining lymph nodes of Batf3−/−mice expressed significantly reduced levels of Ki67, CD25, and T-bet. These results underscore a specific role for Batf3-dependent DCs in regulating priming and expansion of effector CD8+T cells necessary for host resistance against acute respiratory VacV infection.IMPORTANCEDuring respiratory infection with vaccinia virus (VacV), a member ofPoxviridaefamily, CD8+T cells play important role in resolving the primary infection. Effector CD8+T cells clear the virus by accumulating in the infected lungs in large numbers and secreting molecules such as IFN-γ that kill virally infected cells. However, precise cell types that regulate the generation of effector CD8+T cells in the lungs are not well defined. Dendritic cells (DCs) are a heterogeneous population of immune cells that are recognized as key initiators and regulators of T-cell-mediated immunity. In this study, we reveal that a specific subset of DCs that are dependent on the transcription factor Batf3 for their development regulate the magnitude of CD8+T cell effector responses in the lungs, thereby providing protection during pulmonary VacV infection.

scholarly journals Peripheral T-Cell Reactivity to Heat Shock Protein 70 and Its Cofactor GrpE from Tropheryma whipplei Is Reduced in Patients with Classical Whipple's Disease

2017 ◽  
Vol 85 (8) ◽  
Author(s):  
Lucia Trotta ◽  
Kathleen Weigt ◽  
Katina Schinnerling ◽  
Anika Geelhaar-Karsch ◽  
Gerrit Oelkers ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
T Cell Responses ◽  
Tropheryma Whipplei ◽  
Content Type ◽  
Cell Responses ◽  
Ifn Γ

ABSTRACT Classical Whipple's disease (CWD) is characterized by the lack of specific Th1 response toward Tropheryma whipplei in genetically predisposed individuals. The cofactor GrpE of heat shock protein 70 (Hsp70) from T. whipplei was previously identified as a B-cell antigen. We tested the capacity of Hsp70 and GrpE to elicit specific proinflammatory T-cell responses. Peripheral mononuclear cells from CWD patients and healthy donors were stimulated with T. whipplei lysate or recombinant GrpE or Hsp70 before levels of CD40L, CD69, perforin, granzyme B, CD107a, and gamma interferon (IFN-γ) were determined in T cells by flow cytometry. Upon stimulation with total bacterial lysate or recombinant GrpE or Hsp70 of T. whipplei, the proportions of activated effector CD4+ T cells, determined as CD40L+ IFN-γ+, were significantly lower in patients with CWD than in healthy controls; CD8+ T cells of untreated CWD patients revealed an enhanced activation toward unspecific stimulation and T. whipplei-specific degranulation, although CD69+ IFN-γ+ CD8+ T cells were reduced upon stimulation with T. whipplei lysate and recombinant T. whipplei-derived proteins. Hsp70 and its cofactor GrpE are immunogenic in healthy individuals, eliciting effective responses against T. whipplei to control bacterial spreading. The lack of specific T-cell responses against these T. whipplei-derived proteins may contribute to the pathogenesis of CWD.

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