Human T-Cell Responses to the Glucosyltransferases of Streptococcus mutans

ABSTRACT We previously reported differential humoral responses to glucosyltransferases (GTFs), with significantly higher saliva and serum antibody levels to GtfD than to GtfB or GtfC. To test the hypothesis that cellular immune responses to these molecules also may differ, peripheral blood mononuclear cell (PBMC) and T-cell proliferative responses in young adults and children with distinct genetic backgrounds were determined using purified recombinant GtfC and GtfD. PBMCs from all of the volunteers responded to GtfC and -D, but responses were directed predominantly towards GtfD and were major histocompatibility class II antigen dependent. A predominant T-cell response to GtfD, over GtfC, was detectable at various antigen concentrations ranging from 1 to 20 μg/ml and correlated with the differential serum immunoglobulin G (IgG) and salivary IgA antibody responses to the GTFs. Therefore, in naturally sensitized humans,Streptococcus mutans GTFs stimulate differential humoral and cellular immune responses, with the secreted form of GtfD eliciting a stronger response than the cell wall-associated form of GtfC.

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Correlates of T-cell–mediated viral control and phenotype of CD8+ T cells in HIV-2, a naturally contained human retroviral infection

Blood ◽

10.1182/blood-2012-12-472787 ◽

2013 ◽

Vol 121 (21) ◽

pp. 4330-4339 ◽

Cited By ~ 36

Author(s):

Thushan I. de Silva ◽

Yanchun Peng ◽

Aleksandra Leligdowicz ◽

Irfan Zaidi ◽

Lucy Li ◽

...

Keyword(s):

T Cell ◽

Immune Responses ◽

Cd8 T Cells ◽

T Cell Response ◽

Viral Control ◽

Retroviral Infection ◽

Cellular Immune Responses ◽

Key Points ◽

Cellular Immune ◽

Insight Into

Key PointsHIV-2 viral control is associated with a polyfunctional Gag-specific CD8+ T-cell response but not with perforin upregulation. Our findings provide insight into cellular immune responses associated with a naturally contained human retroviral infection.

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Impaired Cellular Immune Responses During the First Week of Severe Acute Influenza Infection

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa226 ◽

2020 ◽

Vol 222 (7) ◽

pp. 1235-1244 ◽

Cited By ~ 4

Author(s):

Jackson S Turner ◽

Tingting Lei ◽

Aaron J Schmitz ◽

Aaron Day ◽

José Alberto Choreño-Parra ◽

...

Keyword(s):

Mechanical Ventilation ◽

T Cell ◽

Immune Responses ◽

Influenza Infection ◽

Cd8 T Cell ◽

T Cell Response ◽

Cell Responses ◽

Cellular Immune Responses ◽

Inflammatory Monocytes ◽

Cellular Immune

Abstract Background Cellular immune responses are not well characterized during the initial days of acute symptomatic influenza infection. Methods We developed a prospective cohort of human subjects with confirmed influenza illness of varying severity who presented within a week after symptom onset. We characterized lymphocyte and monocyte populations as well as antigen-specific CD8+ T-cell and B-cell responses from peripheral blood mononuclear cells using flow cytometry and enzyme-linked immunospot assays. Results We recruited 68 influenza-infected individuals on average 3.5 days after the onset of symptoms. Three patients required mechanical ventilation. Influenza-specific CD8+ T-cell responses expanded before the appearance of plasmablast B cells. However, the influenza-specific CD8+ T-cell response was lower in infected subjects than responses seen in uninfected control subjects. Circulating populations of inflammatory monocytes were increased in most subjects compared with healthy controls. Inflammatory monocytes were significantly reduced in the 3 subjects requiring mechanical ventilation. Inflammatory monocytes were also reduced in a separate validation cohort of mechanically ventilated patients. Conclusions Antigen-specific CD8+ T cells respond early during acute influenza infection at magnitudes that are lower than responses seen in uninfected individuals. Circulating inflammatory monocytes increase during acute illness and low absolute numbers are associated with very severe disease.

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Uninfected erythrocytes inhibit Plasmodium falciparum–induced cellular immune responses in whole-blood assays

Blood ◽

10.1182/blood-2003-08-2867 ◽

2004 ◽

Vol 103 (8) ◽

pp. 3084-3092 ◽

Cited By ~ 9

Author(s):

Siske S. Struik ◽

Fakhreldin M. Omer ◽

Katerina Artavanis-Tsakonas ◽

Eleanor M. Riley

Keyword(s):

T Cell ◽

Immune Responses ◽

Whole Blood ◽

Peripheral Blood ◽

Blood Monocytes ◽

Peripheral Blood Mononuclear ◽

Antigen Uptake ◽

Cellular Immune Responses ◽

Cellular Immune

Abstract Whole-blood assays (WBAs) have been successfully used as a simple tool for immuno-epidemiological field studies evaluating cellular immune responses to mycobacterial and viral antigens. Rather unexpectedly, we found very poor cytokine responses to malaria antigens in WBAs in 2 immuno-epidemiological studies carried out in malaria endemic populations in Africa. We have therefore conducted a detailed comparison of cellular immune responses to live (intact) and lysed malaria-infected erythrocytes in WBAs and in peripheral blood mononuclear cell (PBMC) cultures. We observed profound inhibition of both proliferative and interferon-γ responses to malarial antigens in WBAs as compared with PBMC cultures. This inhibition was seen only for malaria antigens and could not be overcome by increasing either antigen concentration or responder cell numbers. Inhibition was mediated by intact erythrocytes and occurred early in the culture period, suggesting that failure of antigen uptake might underlie the lack of T-cell responses. In support of this hypothesis, we have shown that intact uninfected erythrocytes specifically inhibit phagocytosis of infected red blood cells by peripheral blood monocytes. We propose that specific biochemical interactions with uninfected erythrocytes inhibit the phagocytosis of malaria-infected erythrocytes and that this may impede T-cell recognition in vivo. (Blood. 2004; 103:3084-3092)

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Induction of Specific Immune Responses by Severe Acute Respiratory Syndrome Coronavirus Spike DNA Vaccine with or without Interleukin-2 Immunization Using Different Vaccination Routes in Mice

Clinical and Vaccine Immunology ◽

10.1128/cvi.00019-07 ◽

2007 ◽

Vol 14 (7) ◽

pp. 894-901 ◽

Cited By ~ 19

Author(s):

Hui Hu ◽

Xinya Lu ◽

Ling Tao ◽

Bingke Bai ◽

Zhenfeng Zhang ◽

...

Keyword(s):

T Cell ◽

Severe Acute Respiratory Syndrome ◽

Immune Responses ◽

Antibody Response ◽

Dna Vaccine ◽

Cell Response ◽

Interleukin 2 ◽

T Cell Response ◽

Cellular Immune Responses ◽

Cellular Immune

ABSTRACT DNA vaccines induce humoral and cellular immune responses in animal models and humans. To analyze the immunogenicity of the severe acute respiratory syndrome (SARS) coronavirus (CoV), SARS-CoV, spike DNA vaccine and the immunoregulatory activity of interleukin-2 (IL-2), DNA vaccine plasmids pcDNA-S and pcDNA-IL-2 were constructed and inoculated into BALB/c mice with or without pcDNA-IL-2 by using three different immunization routes (the intramuscular route, electroporation, or the oral route with live attenuated Salmonella enterica serovar Typhimurium). The cellular and humoral immune responses were assessed by enzyme-linked immunosorbent assays, lymphocyte proliferation assays, enzyme-linked immunospot assays, and fluorescence-activated cell sorter analyses. The results showed that specific humoral and cellular immunities could be induced in mice by inoculating them with SARS-CoV spike DNA vaccine alone or by coinoculation with IL-2-expressing plasmids. In addition, the immune response levels in the coinoculation groups were significantly higher than those in groups receiving the spike DNA vaccine alone. The comparison between the three vaccination routes indicated that oral vaccination evoked a vigorous T-cell response and a weak response predominantly with subclass immunoglobulin G2a (IgG2a) antibody. However, intramuscular immunization evoked a vigorous antibody response and a weak T-cell response, and vaccination by electroporation evoked a vigorous response with a predominant subclass IgG1 antibody response and a moderate T-cell response. Our findings show that the spike DNA vaccine has good immunogenicity and can induce specific humoral and cellular immunities in BALB/c mice, while IL-2 plays an immunoadjuvant role and enhances the humoral and cellular immune responses. Different vaccination routes also evoke distinct immune responses. This study provides basic information for the design of DNA vaccines against SARS-CoV.

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Interdependencies of cellular and humoral immune responses in heterologous and homologous SARS‑CoV‑2 vaccination

10.22541/au.164040480.07315088/v1 ◽

2021 ◽

Author(s):

Luise Erpenbeck ◽

Moritz M. Hollstein ◽

Lennart Münsterkötter ◽

Michael Schön ◽

Armin Bergmann ◽

...

Keyword(s):

T Cell ◽

Immune Responses ◽

T Cell Activation ◽

Neutralizing Antibodies ◽

Cell Activation ◽

Booster Vaccination ◽

Interferon Γ ◽

T Cell Response ◽

Cellular Immune Responses ◽

Cellular Immune

Background: Homologous and heterologous SARS-CoV-2 vaccinations yield different spike protein-directed humoral and cellular immune responses. This study aimed to explore their currently unknown interdependencies. Methods: COV-ADAPT is a prospective, observational cohort study of 417 healthcare workers who received vaccination with homologous ChAdOx1 nCoV-19, homologous BNT162b2 or with heterologous ChAdOx1 nCoV-19/BNT162b2. We assessed humoral (anti-spike-RBD-IgG, neutralizing antibodies, avidity) and cellular (spike-induced T cell interferon‑γ release) immune responses in blood samples up to 2 weeks before (T1) and 2 to 12 weeks following secondary immunization (T2). Results: Initial vaccination with ChAdOx1 nCoV-19 resulted in lower anti-spike-RBD-IgG compared to BNT162b2 (70±114 vs. 226±279 BAU/ml, p<0.01) at T1. Booster vaccination with BNT162b2 proved superior to ChAdOx1 nCoV-19 at T2 (anti-spike-RBD-IgG: ChAdOx1 nCoV-19/BNT162b2 2387±1627 and homologous BNT162b2 3202±2184 vs. homologous ChAdOx1 nCoV-19 413±461 BAU/ml, both p<0.001; spike-induced T cell interferon-γ release: ChAdOx1 nCoV-19/BNT162b2 5069±6733 and homologous BNT162b2 4880±7570 vs. homologous ChAdOx1 nCoV-19 1152±2243 mIU/ml, both p<0.001). No significant differences were detected between BNT162b2-boostered groups at T2. For ChAdOx1 nCoV-19, no booster effect on T cell activation could be observed. We found associations between anti-spike-RBD-IgG levels (ChAdOx1 nCoV-19/BNT162b2 and homologous BNT162b2) and T cell responses (homologous ChAdOx1 nCoV-19 and ChAdOx1 nCoV-19/BNT162b2) from T1 to T2. Additionally, anti-spike-RBD-IgG and T cell response were linked at both time points (all groups combined). All regimes yielded neutralizing antibodies and increased antibody avidity at T2. Conclusions: Interdependencies between humoral and cellular immune responses differ between common SARS-CoV-2 vaccination regimes. T cell activation is unlikely to compensate for poor humoral responses.

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In Silico Defined SARS-CoV2 Epitopes May Not Predict Immunogenicity to COVID19

10.1101/2021.07.08.451555 ◽

2021 ◽

Author(s):

Ke Pan ◽

Yulun Chiu ◽

Michelle Chen ◽

Junmei Wang ◽

Ivy Lai ◽

...

Keyword(s):

T Cell ◽

In Silico ◽

T Cell Responses ◽

T Cell Response ◽

Binding Affinities ◽

Cell Responses ◽

Cellular Immune Responses ◽

Humoral Responses ◽

Cellular Immune ◽

In Silico Methods

SARS-CoV-2 infections elicit both humoral and cellular immune responses. For the prevention and treatment of COVID19, the disease caused by SARS-CoV-2, it has become increasingly apparent that T cell responses are equally, if not more important than humoral responses in mediating recovery and immune-protection. One of the major challenges in developing T cell-based therapies for infectious and malignant diseases has been the identification of immunogenic epitopes that can elicit a meaningful T cell response. Traditionally, this has been achieved using sophisticated in silico methods to predict putative epitopes deduced from binding affinities and consensus data. Our studies find that, in contrast to current dogma, immunodominant SARS-CoV-2 peptides defined by such in silico methods often fail to elicit T cell responses recognizing naturally presented SARS-CoV-2 epitopes.

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Baseline Levels of Influenza-Specific B Cells and T Cell Responses Modulate Human Immune Responses to Swine Variant Influenza A/H3N2 Vaccine

Vaccines ◽

10.3390/vaccines8010126 ◽

2020 ◽

Vol 8 (1) ◽

pp. 126

Author(s):

Lilin Lai ◽

Nadine Rouphael ◽

Yongxian Xu ◽

Amy C. Sherman ◽

Srilatha Edupuganti ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Immune Responses ◽

Influenza A ◽

Vaccine Dose ◽

T Cell Responses ◽

Post Vaccination ◽

Cell Responses ◽

Cellular Immune Responses ◽

Cellular Immune

The cellular immune responses elicited by an investigational vaccine against an emergent variant of influenza (H3N2v) are not fully understood. Twenty-five subjects, enrolled in an investigational influenza A/H3N2v vaccine study, who received two doses of vaccine 21 days apart, were included in a sub-study of cellular immune responses. H3N2v-specific plasmablasts were determined by ELISpot 8 days after each vaccine dose and H3N2v specific CD4+ T cells were quantified by intracellular cytokine and CD154 (CD40 ligand) staining before vaccination, 8 and 21 days after each vaccine dose. Results: 95% (19/20) and 96% (24/25) subjects had pre-existing H3N2v specific memory B, and T cell responses, respectively. Plasmablast responses at Day 8 after the first vaccine administration were detected against contemporary H3N2 strains and correlated with hemagglutination inhibition HAI (IgG: p = 0.018; IgA: p < 0.001) and Neut (IgG: p = 0.038; IgA: p = 0.021) titers and with memory B cell frequency at baseline (IgA: r = 0.76, p < 0.001; IgG: r = 0.74, p = 0.0001). The CD4+ T cells at Days 8 and 21 expanded after prime vaccination and this expansion correlated strongly with early post-vaccination HAI and Neut titers (p ≤ 0.002). In an adult population, the rapid serological response observed after initial H3N2v vaccination correlates with post-vaccination plasmablasts and CD4+ T cell responses.

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Immune responses during gestational malaria: a review of the current knowledge and future trend of research

The Journal of Infection in Developing Countries ◽

10.3855/jidc.3777 ◽

2014 ◽

Vol 8 (04) ◽

pp. 391-402 ◽

Cited By ~ 8

Author(s):

Amanda Maestre ◽

Jaime Carmona-Fonseca

Keyword(s):

Immune Responses ◽

Current Knowledge ◽

Placental Malaria ◽

Future Trend ◽

Maternal Infection ◽

Variant Surface Antigens ◽

Cellular Immune Responses ◽

First Child ◽

Humoral Responses ◽

Cellular Immune

Women pregnant with their first child are susceptible to severe P. falciparum disease from placental malaria because they lack immunity to placenta-specific cytoadherence proteins. In subsequent pregnancies, as immunity against placental parasites is acquired, there is a reduced risk of adverse effects of malaria on the mother and fetus and asymptomatic parasitaemia is common. In the case of vivax malaria, with increasing reports of severe cases in Asia and South America, the effects of infection by this species during pregnancy remain to be elucidated. This review summarized the main aspects involved in the acquisition of specific antimalarial immune responses during pregnancy with emphasis in research carried out in America and Asia, in order to offer a framework of interpretation for studies on pregnant women with malaria which are recently being produced in these regions. The authors conclude that (1) Effective humoral responses during gestational malaria are mainly directed against variant surface antigens codified by genes of the var2Csa family of P. falciparum; (2) Acquisition of immunity against these variant antigens depends on the degree and intensity of transmission, and the chance increases with age and successive pregnancies; (3) Antibody development is guided by specific cellular immune responses in cases of placental and maternal infection, and (4) The study of the significance of acquisition of specific immunity against both P. falciparum and P. vivax in America, should be performed.

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Humoral and Cellular Immune Responses to Trypanosoma cruzi-Derived Paraflagellar Rod Proteins in Patients with Chagas' Disease

Infection and Immunity ◽

10.1128/iai.71.6.3165-3171.2003 ◽

2003 ◽

Vol 71 (6) ◽

pp. 3165-3171 ◽

Cited By ~ 34

Author(s):

Vladimir Michailowsky ◽

Keith Luhrs ◽

Manoel Otávio C. Rocha ◽

David Fouts ◽

Ricardo T. Gazzinelli ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Immune Responses ◽

Chagas Disease ◽

Mononuclear Cells ◽

Clinical Symptoms ◽

Cellular Responses ◽

Peripheral Blood Mononuclear ◽

Cellular Immune Responses ◽

Ifn Γ ◽

Cellular Immune

ABSTRACT Sera and peripheral blood mononuclear cells (PBMC) from patients displaying different clinical symptoms as well as from normal uninfected individuals (NI) were used to evaluate the humoral and cellular responses of Chagas' disease patients to Trypanosoma cruzi-derived paraflagellar rod proteins (PFR). Our results show that sera from both asymptomatic Chagas' disease patients (ACP) and cardiac Chagas' disease patients (CCP) have higher levels of antibodies to PFR than sera from NI. Immunoglobulin G1 (IgG1) and IgG3 were the main Ig isotypes that recognized PFR. We also tested three recombinant forms of PFR, named rPAR-1, rPAR-2, and rPAR-3, by Western blot analysis. Sera from seven out of eight patients with Chagas' disease recognized one of the three rPAR forms. Sera from 75, 50, and 37.5% of Chagas' disease patients tested recognized rPAR-3, rPAR-2, and rPAR-1, respectively. PFR induced proliferation of 100 and 70% of PBMC from ACP and CCP, respectively. Further, stimulation of cells from Chagas' disease patients with PFR enhanced the frequencies of both small and large CD4+ CD25+ and CD4+ CD69+ lymphocytes, as well as that of small CD8+ CD25+ lymphocytes. Finally, we evaluated the ability of PFR to elicit the production of gamma interferon (IFN-γ) by PBMC from patients with Chagas' disease. Fifty percent of the PBMC from ACP as well as CCP produced IFN-γ upon stimulation with PFR. PFR enhanced the percentages of IFN-γ-producing cells in both CD3+ and CD3− populations. Within the T-cell population, large CD4+ T lymphocytes were the main source of IFN-γ.

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