scholarly journals CHARM: COVID-19 Health Action Response for Marines – association of antigen-specific interferon-gamma and IL2 responses with asymptomatic and symptomatic infections after a positive qPCR SARS-CoV-2 test

2021 ◽  
Author(s):  
Martha Sedegah ◽  
Chad Porter ◽  
Michael R. Hollingdale ◽  
Harini Ganeshan ◽  
Jun Huang ◽  
...  
Keyword(s):  
T Cell ◽  
Interferon Gamma ◽  
T Cell Responses ◽  
Cell Mediated Immunity ◽  
N Protein ◽  
Cell Responses ◽  
M Proteins ◽  
Health Action ◽  
Ifn Γ ◽  
N Pool

SARS-CoV-2 T cell responses are associated with COVID-19 recovery, and Class I- and Class II-restricted epitopes have been identified in the spike (S), nucleocapsid (N) and membrane (M) proteins and others. This prospective COVID-19 Health Action Response for Marines (CHARM) study enabled assessment of T cell responses in symptomatic and asymptomatic SARS-CoV-2 infected participants. At enrollment all participants were negative by qPCR; follow-up occurred biweekly and then bimonthly for the next 6 weeks. Study participants who tested positive by qPCR SARS-CoV-2 test were asked to enroll in an immune response sub-study. FluoroSpot interferon-gamma (IFN-γ) and IL2 responses following qPCR-confirmed infection at enrollment (day 0), day 7 and 14 and more than 28 days later were measured using pools of 17mer peptides covering S, N, and M proteins, or CD4+CD8 peptide pools containing predicted epitopes from multiple SARS-CoV-2 antigens. Among 124 asymptomatic and 105 symptomatic participants, SARS-CoV-2 infection generated IFN-γ responses to the S, N and M proteins that persisted longer in asymptomatic cases. IFN-γ responses were significantly (p=0.001) more frequent to the N pool (51.4%) than the M pool (18.9%) among asymptomatic subjects; however, the difference was not statistically significant (p=0.06) for symptomatic subjects (N pool: 44.4%; M pool: 25.9%). In asymptomatic participants IFN-γ responders to the CD4+CD8 pool responded more frequently to the S pool (55.6%) and N pool (57.1%), than the M pool (7.1%), but symptomatic participants, IFN-γ responses were more frequent to the S pool (75.0%) than N pool (33.3%) and M pool (33.3%). The frequencies of IFN-γ responses to the S and N+M pools peaked 7 days after the positive qPCR test among asymptomatic (S pool: 22.2%; N+M pool: 28.7%) and symptomatic (S pool: 15.3%; N+M pool 21.9%) participants and dropped by >28 days. Magnitudes of post-infection IFN-γ and IL2 responses to the N+M pool were significantly correlated with IFN-γ and IL2 responses to the N and M pools. These data further support the central role of Th1-biased cell mediated immunity IFN-γ and IL2 responses, particularly to the N protein, in controlling COVID-19 symptoms, and justify T cell-based COVID-19 vaccines that include the N and S proteins.

scholarly journals T-Cell Responses to the Mycobacterium tuberculosis-Specific Antigen ESAT-6 in Brazilian Tuberculosis Patients

2002 ◽  
Vol 70 (12) ◽  
pp. 6707-6714 ◽  
Author(s):  
Fernando L. L. Cardoso ◽  
Paulo R. Z. Antas ◽  
Alexandre S. Milagres ◽  
Annemieke Geluk ◽  
Kees L. M. C. Franken ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Mononuclear Cells ◽  
Critical Role ◽  
Specific Antigen ◽  
T Cell Responses ◽  
Cell Mediated Immunity ◽  
Cell Responses ◽  
Leprosy Patients ◽  
Ifn Γ

ABSTRACT The Mycobacterium tuberculosis-specific ESAT-6 antigen induces highly potent T-cell responses and production of gamma interferon (IFN-γ), which play a critical role in protective cell-mediated immunity against tuberculosis (TB). In the present study, IFN-γ secretion by peripheral blood mononuclear cells (PBMCs) in response to M. tuberculosis ESAT-6 in Brazilian TB patients was investigated in relation to clinical disease types, such as pleurisy and cavitary pulmonary TB. Leprosy patients, patients with pulmonary diseases other than TB, and healthy donors were assayed as control groups. Sixty percent of the TB patients indeed recognized M. tuberculosis ESAT-6, as did 50% of the leprosy patients and 60% of the non-TB controls. Nevertheless, the levels of IFN-γ in response to the antigen ESAT, but not to antigen 85B (Ag85B) and purified protein derivative (PPD), were significantly lower in controls than in patients with treated TB or pleural or cavitary TB. Moreover, according to Mycobacterium bovis BCG vaccination status, only 59% of the vaccinated TB patients responded to ESAT in vitro, whereas 100% of them responded to PPD. Both CD4 and CD8 T cells were able to release IFN-γ in response to ESAT. The present data demonstrate the specificity of ESAT-6 of M. tuberculosis and its ability to discriminate TB patients from controls, including leprosy patients. However, to obtain specificity, it is necessary to include quantitative IFN-γ production in response to the antigen as well, and this might limit the use of ESAT-6-based immunodiagnosis of M. tuberculosis infection in an area of TB endemicity.

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.

scholarly journals IFN-γ and IL-10 islet-antigen-specific T cell responses in autoantibody-negative first-degree relatives of patients with type 1 diabetes

Diabetologia ◽  
2010 ◽  
Vol 53 (7) ◽  
pp. 1451-1460 ◽  
Author(s):  
L. G. Petrich de Marquesini ◽  
J. Fu ◽  
K. J. Connor ◽  
A. J. Bishop ◽  
N. E. McLintock ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
T Cell Responses ◽  
Cell Responses ◽  
First Degree Relatives ◽  
Ifn Γ ◽  
Islet Antigen

scholarly journals PD-L1 – PD-1 interactions limit effector Treg cell populations at homeostasis and during infection

2020 ◽  
Author(s):  
J.A. Perry ◽  
J.T. Clark ◽  
J. Gullicksrud ◽  
J. DeLong ◽  
L. Shallberg ◽  
...  
Keyword(s):  
T Cell ◽  
Treg Cell ◽  
Cell Activity ◽  
T Cell Responses ◽  
Treg Cells ◽  
Whole Body ◽  
Cell Responses ◽  
Early Production ◽  
Ifn Γ ◽  
Specific Deletion

AbstractWhile much is known about the factors that promote the development of diverse Treg cell responses, less is known about the pathways that constrain Treg cell activities. The studies presented here reveal that at homeostasis there is a population of effector Treg cells that express PD-1, and that blockade of PD-L1 or loss of PD-1 results in increased Treg cell activity. In response to infection with the parasite T. gondii, the early production of IFN-γ results in widespread upregulation of PD-L1. Moreover, blockade of PD-L1, whole body deletion of PD-1, or lineage-specific deletion of PD-1 in Foxp3+ cells prevented the loss of the effector Treg cells but resulted in reduced pathogen specific CD4+ T cell responses during infection. Thus, at homeostasis basal PD-L1 expression constrains and tunes the pool of Treg cells, but during infection the upregulation of PD-L1 provides a mechanism to contract the Treg cell population required to maximize the development of pathogen specific CD4+ T cell responses.

Nitric oxide-producing CD11b+Ly-6G(Gr-1)+CD31(ER-MP12)+cells in the spleen of cyclophosphamide–treated mice: implications for T-cell responses in immunosuppressed mice

Blood ◽  
2000 ◽  
Vol 95 (1) ◽  
pp. 212-220 ◽  
Author(s):  
Iñigo Angulo ◽  
Federico Gómez de las Heras ◽  
José F. Garcı́a-Bustos ◽  
Domingo Gargallo ◽  
M. Angeles Muñoz-Fernández ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Proliferation ◽  
T Cell ◽  
T Cell Responses ◽  
T Cell Proliferation ◽  
Intensive Chemotherapy ◽  
Suppressive Activity ◽  
Cell Responses ◽  
Nos Inhibitors ◽  
Ifn Γ

Abstract During recovery from intensive chemotherapy with cyclophosphamide (CTX), mice suffer a severe but transitory impairment in spleen cell proliferation to T-cell mitogens (Con A or anti-CD3 plus IL-2). Although CTX treatment reduced spleen T-cell cellularity, this cannot fully account for T-cell unresponsiveness. The results showed that CTX induces the colonization of spleen by an immature myeloid CD11b+Ly-6G+CD31+ population. Its presence closely correlated with the maximum inhibition of T-cell proliferation. Moreover, this suppressive activity was dependent on nitric oxide (NO) production in cultures since (1) higher amounts of nitric oxide and inducible nitric oxide synthase (iNOS) mRNA were produced in CTX spleen cells (CTX-SC) than in control splenocyte cultures and (2) NOS inhibitors greatly improved the proliferation of T lymphocytes. Nitric oxide production and suppressive activity were also dependent on endogenous interferon-γ (IFN-γ) production since anti–IFN-γ abrogated both effects. Finally, iNOS protein expression was restricted to a heterogeneous population of CD31+cells in which CD11b+Ly-6G+ cells were required to suppress T-cell proliferation. These results indicated that CTX might also cause immunosuppression by a mechanism involving the presence of immature myeloid cells with suppressor activity. This may have implications in clinical praxis since inappropriate immunotherapies in patients treated with intensive chemotherapy could lead to deleterious T-cell responses. (Blood. 2000;95:212-220)

scholarly journals Enhanced T Cell Responses Induced by a Necrotic Dendritic Cell Vaccine, Expressing HCV NS3

2020 ◽  
Vol 11 ◽  
Author(s):  
Zelalem A. Mekonnen ◽  
Makutiro G. Masavuli ◽  
Wenbo Yu ◽  
Jason Gummow ◽  
Dawn M. Whelan ◽  
...  
Keyword(s):  
T Cell ◽  
Vaccination Strategy ◽  
T Cell Responses ◽  
Dendritic Cell Vaccine ◽  
Effector Memory ◽  
Cell Vaccine ◽  
Cell Mediated Immunity ◽  
Structural Protein ◽  
Cell Responses ◽  
Dc Vaccine

A vaccine that induces potent, broad and sustained cell-mediated immunity, resulting in effective memory has the potential to restrict hepatitis C (HCV) virus infection. Early, multi-functional CD4+ and CD8+ T cell responses against non-structural protein 3 (NS3) have been associated with HCV clearance. Necrotic cells generate strong immune responses and represent a major antigenic source used by dendritic cells (DC) for processing and presentation, but there is conflicting evidence as to their immunogenicity in vaccination. Immunization with DC loaded with viral antigens has been done in the past, but to date the immunogenicity of live vs. necrotic DC vaccines has not been investigated. We developed a DC2.4 cell line stably expressing HCV NS3, and compared the NS3-specific responses of live vs. necrotic NS3 DC. Vaccination of mice with necrotic NS3 DC increased the breadth of T-cell responses and enhanced the production of IL-2, TNF-α, and IFN-γ by effector memory CD4+ and CD8+T cells, compared to mice vaccinated with live NS3 DC. A single dose of necrotic NS3 DC vaccine induced a greater influx and activation of cross-presenting CD11c+ CD8α+ DC and necrosis-sensing Clec9A+ DC in the draining lymph nodes. Furthermore, using a hydrodynamic challenge model necrotic NS3 DC vaccination resulted in enhanced clearance of NS3-positive hepatocytes from the livers of vaccinated mice. Taken together, the data demonstrate that necrotic DC represent a novel and exciting vaccination strategy capable of inducing broad and multifunctional T cell memory.

scholarly journals Priming with Recombinant BCG Expressing HTI Enhances the Magnitude and Breadth of the T-Cell Immune Responses Elicited by MVA.HTI in BALB/c Mice

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 678
Author(s):  
Narcís Saubi ◽  
Athina Kilpeläinen ◽  
Yoshiki Eto ◽  
Chun-Wei Chen ◽  
Àlex Olvera ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Vaccine Platform ◽  
Cell Responses ◽  
Total Magnitude ◽  
T Cell Immune Responses ◽  
Ifn Γ ◽  
Hiv 1 ◽  
Recombinant Bcg

The use of Mycobacterium bovis bacillus Calmette–Guérin (BCG) as a live vaccine vehicle is a promising approach for HIV-1-specific T-cell induction. In this study, we used recombinant BCG expressing HIVACAT T-cell immunogen (HTI), BCG.HTI2auxo.int. BALB/c mice immunization with BCG.HTI2auxo.int prime and MVA.HTI boost was safe and induced HIV-1-specific T-cell responses. Two weeks after boost, T-cell responses were assessed by IFN-γ ELISpot. The highest total magnitude of IFN-γ spot-forming cells (SFC)/106 splenocytes was observed in BCG.HTI2auxo.int primed mice compared to mice receiving MVA.HTI alone or mice primed with BCGwt, although the differences between the vaccination regimens only reached trends. In order to evaluate the differences in the breadth of the T-cell immune responses, we examined the number of reactive peptide pools per mouse. Interestingly, both BCG.HTI2auxo.int and BCGwt primed mice recognized an average of four peptide pools per mouse. However, the variation was higher in BCG.HTI2auxo.int primed mice with one mouse recognizing 11 peptide pools and three mice recognizing few or no peptide pools. The recognition profile appeared to be more spread out for BCG.HTI2auxo.int primed mice and mice only receiving MVA.HTI. Here, we describe a useful vaccine platform for priming protective responses against HIV-1/TB and other prevalent infectious diseases.

scholarly journals Naturally Exposed Populations Differ in Their T1 and T2 Responses to the Circumsporozoite Protein of Plasmodium falciparum

2002 ◽  
Vol 70 (3) ◽  
pp. 1468-1474 ◽  
Author(s):  
W. H. H. Reece ◽  
M. Plebanski ◽  
P. Akinwunmi ◽  
P. Gothard ◽  
K. L. Flanagan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
T Cell ◽  
Affect Regulation ◽  
Elispot Assay ◽  
T Cell Responses ◽  
Circumsporozoite Protein ◽  
Interleukin 4 ◽  
Cell Responses ◽  
Ifn Γ ◽  
T1 And T2

ABSTRACT T-cell responses directed against the circumsporozoite protein (CS) of Plasmodium falciparum can mediate protection against malaria. We determined the frequency of T cells reactive to different regions of the CS in the blood of donors naturally exposed to P. falciparum by examining T1 (gamma interferon [IFN-γ] ELISPOT assay), T2 (interleukin 4 [IL-4] ELISPOT assay), and proliferative T-cell responses. The proliferative responses were weak, which confirmed previous observations. The responses to the CS in the IL-4 and IFN-γ ELISPOT assays were also weak (<40 responding cells per 106 cells), much weaker than the response to the purified protein derivative of Mycobacterium tuberculosis in the same donors. Moreover, a response in one assay could not be used to predict a response in either of the other assays, suggesting that although these assays may measure different responding cells, all of the responses are weakly induced by natural exposure. Interestingly, the two different study populations used had significantly different T1 and T2 biases in their responses in the C terminus of the protein, suggesting that the extent of P. falciparum exposure can affect regulation of the immune system.

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