scholarly journals Roles of IFN-γ and γδ T Cells in Protective Immunity Against Blood-Stage Malaria

2013 ◽  
Vol 4 ◽  
Author(s):  
Shin-Ichi Inoue ◽  
Mamoru Niikura ◽  
Shoichiro Mineo ◽  
Fumie Kobayashi
Keyword(s):  
T Cells ◽  
Protective Immunity ◽  
Γδ T Cells ◽  
Blood Stage ◽  
Ifn Γ ◽  
Blood Stage Malaria

scholarly journals Cytotoxic activities of CD8+ T cells collaborate with macrophages to protect against blood-stage murine malaria

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Takashi Imai ◽  
Hidekazu Ishida ◽  
Kazutomo Suzue ◽  
Tomoyo Taniguchi ◽  
Hiroko Okada ◽  
...  
Keyword(s):  
T Cells ◽  
Mhc Class I ◽  
Cd8 T Cells ◽  
Protective Immunity ◽  
Molecular Mechanisms ◽  
Blood Stage ◽  
Class I ◽  
Cytotoxic Activities ◽  
Dependent Manner ◽  
Blood Stage Malaria

The protective immunity afforded by CD8+ T cells against blood-stage malaria remains controversial because no MHC class I molecules are displayed on parasite-infected human erythrocytes. We recently reported that rodent malaria parasites infect erythroblasts that express major histocompatibility complex (MHC) class I antigens, which are recognized by CD8+ T cells. In this study, we demonstrate that the cytotoxic activity of CD8+ T cells contributes to the protection of mice against blood-stage malaria in a Fas ligand (FasL)-dependent manner. Erythroblasts infected with malarial parasites express the death receptor Fas. CD8+ T cells induce the externalization of phosphatidylserine (PS) on the infected erythroblasts in a cell-to-cell contact-dependent manner. PS enhances the engulfment of the infected erythroid cells by phagocytes. As a PS receptor, T-cell immunoglobulin-domain and mucin-domain-containing molecule 4 (Tim-4) contributes to the phagocytosis of malaria-parasite-infected cells. Our findings provide insight into the molecular mechanisms underlying the protective immunity exerted by CD8+ T cells in collaboration with phagocytes.

scholarly journals Parasite-Specific CD4+IFN-γ+IL-10+T Cells Distribute within Both Lymphoid and Nonlymphoid Compartments and Are Controlled Systemically by Interleukin-27 and ICOS during Blood-Stage Malaria Infection

2015 ◽  
Vol 84 (1) ◽  
pp. 34-46 ◽  
Author(s):  
Ana Villegas-Mendez ◽  
Tovah N. Shaw ◽  
Colette A. Inkson ◽  
Patrick Strangward ◽  
J. Brian de Souza ◽  
...  
Keyword(s):  
T Cells ◽  
Malaria Infection ◽  
Fluorescent Protein ◽  
Yellow Fluorescent Protein ◽  
Interleukin 10 ◽  
Plasmodium Yoelii ◽  
Blood Stage ◽  
Content Type ◽  
Ifn Γ ◽  
Blood Stage Malaria

Immune-mediated pathology in interleukin-10 (IL-10)-deficient mice during blood-stage malaria infection typically manifests in nonlymphoid organs, such as the liver and lung. Thus, it is critical to define the cellular sources of IL-10 in these sensitive nonlymphoid compartments during infection. Moreover, it is important to determine if IL-10 production is controlled through conserved or disparate molecular programs in distinct anatomical locations during malaria infection, as this may enable spatiotemporal tuning of the regulatory immune response. In this study, using dual gamma interferon (IFN-γ)–yellow fluorescent protein (YFP) and IL-10–green fluorescent protein (GFP) reporter mice, we show that CD4+YFP+T cells are the major source of IL-10 in both lymphoid and nonlymphoid compartments throughout the course of blood-stagePlasmodium yoeliiinfection. Mature splenic CD4+YFP+GFP+T cells, which preferentially expressed high levels of CCR5, were capable of migrating to and seeding the nonlymphoid tissues, indicating that the systemically distributed host-protective cells have a common developmental history. Despite exhibiting comparable phenotypes, CD4+YFP+GFP+T cells from the liver and lung produced significantly larger quantities of IL-10 than their splenic counterparts, showing that the CD4+YFP+GFP+T cells exert graded functions in distinct tissue locations during infection. Unexpectedly, given the unique environmental conditions within discrete nonlymphoid and lymphoid organs, we show that IL-10 production by CD4+YFP+T cells is controlled systemically during malaria infection through IL-27 receptor signaling that is supported after CD4+T cell priming by ICOS signaling. The results in this study substantially improve our understanding of the systemic IL-10 response to malaria infection, particularly within sensitive nonlymphoid organs.

scholarly journals Cryopreservation of Whole Tumor Biopsies from Rectal Cancer Patients Enable Phenotypic and In Vitro Functional Evaluation of Tumor-Infiltrating T Cells

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2428
Author(s):  
Frank Liang ◽  
Azar Rezapour ◽  
Peter Falk ◽  
Eva Angenete ◽  
Ulf Yrlid
Keyword(s):  
Rectal Cancer ◽  
T Cells ◽  
Γδ T Cells ◽  
T Cell Subsets ◽  
Functional Evaluation ◽  
Mait Cells ◽  
Ifn Γ ◽  
Tumor Biopsies

TILs comprise functionally distinct conventional and unconventional T cell subsets and their role in responses to CRC treatments is poorly understood. We explored recovery of viable TILs from cryopreserved tumor biopsies of (chemo)-radiated patients with rectal cancer to establish a platform for retrospective TIL analyses of frozen tumors from pre-selected study cohorts. Frequencies of TIL subsets and their capacity to mount IFN-γ responses in cell suspensions of fresh vs. cryopreserved portions of the same tumor biopsies were determined for platform validation. The percentages and proportions of CD4+ TILs and CD8+ cytotoxic T lymphocytes (CTLs) among total TILs were not affected by cryopreservation. While recovery of unconventional γδ T cells and mucosal-associated invariant T cells (MAIT cells) was stable after cryopreservation, the regulatory T cells (Tregs) were reduced, but in sufficient yields for quantification. IFN-γ production by in vitro-stimulated CD4+ TILs, CTLs, γδ T cells, and MAIT cells were proportionally similar in fresh and cryopreserved tumor portions, albeit the latter displayed lower levels. Thus, the proposed platform intended for TIL analyses on cryopreserved tumor biobank biopsies holds promises for studies linking the quantity and quality of TIL subsets with specific clinical outcome after CRC treatment.

scholarly journals Circulating CD4 T cells elicited by endemic coronaviruses display vast disparities in abundance and functional potential linked to both antigen specificity and age

2021 ◽  
Author(s):  
Katherine A Richards ◽  
Maryah Glover ◽  
Jeremy C Crawford ◽  
Paul Thomas ◽  
Chantelle White ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Protective Immunity ◽  
Granzyme B ◽  
Antigen Specificity ◽  
Functional Potential ◽  
Membrane Envelope ◽  
Ifn Γ ◽  
Human Coronaviruses ◽  
Repeated Infections

Abstract Repeated infections with endemic human coronaviruses are thought to reflect lack of long-lasting protective immunity. Here, we evaluate circulating human CD4 T cells collected prior to 2020 for reactivity towards hCoV spike proteins, probing for the ability to produce IFN-γ, IL-2 or granzyme B. We find robust reactivity to spike-derived epitopes, comparable to influenza, but highly variable abundance and functional potential across subjects, depending on age and viral antigen specificity. To explore the potential of these memory cells to be recruited in SARS-CoV-2 infection, we examined the same subjects for cross-reactive recognition of epitopes from SARS-CoV-2 nucleocapsid, membrane/envelope, and spike. The functional potential of these cross-reactive CD4 T cells was highly variable, with nucleocapsid-specific CD4 T cells, but not spike-reactive cells showing exceptionally high levels of granzyme production upon stimulation. These results are considered in light of recruitment of hCoV-reactive cells into responses of humans to SARS-CoV infections or vaccinations.

scholarly journals Vaccination with DNA Encoding the Immunodominant LACK Parasite Antigen Confers Protective Immunity to Mice Infected with Leishmania major

1997 ◽  
Vol 186 (7) ◽  
pp. 1137-1147 ◽  
Author(s):  
Sanjay Gurunathan ◽  
David L. Sacks ◽  
Daniel R. Brown ◽  
Steven L. Reiner ◽  
Hughes Charest ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Protective Immunity ◽  
Leishmania Major ◽  
Protective Efficacy ◽  
Dna Vaccination ◽  
Attractive Alternative ◽  
Dna Immunization ◽  
Dna Encoding ◽  
Ifn Γ

To determine whether DNA immunization could elicit protective immunity to Leishmania major in susceptible BALB/c mice, cDNA for the cloned Leishmania antigen LACK was inserted into a euykaryotic expression vector downstream to the cytomegalovirus promoter. Susceptible BALB/c mice were then vaccinated subcutaneously with LACK DNA and challenged with L. major promastigotes. We compared the protective efficacy of LACK DNA vaccination with that of recombinant LACK protein in the presence or absence of recombinant interleukin (rIL)-12 protein. Protection induced by LACK DNA was similar to that achieved by LACK protein and rIL-12, but superior to LACK protein without rIL-12. The immunity conferred by LACK DNA was durable insofar as mice challenged 5 wk after vaccination were still protected, and the infection was controlled for at least 20 wk after challenge. In addition, the ability of mice to control infection at sites distant to the site of vaccination suggests that systemic protection was achieved by LACK DNA vaccination. The control of disease progression and parasitic burden in mice vaccinated with LACK DNA was associated with enhancement of antigen-specific interferon-γ (IFN-γ) production. Moreover, both the enhancement of IFN-γ production and the protective immune response induced by LACK DNA vaccination was IL-12 dependent. Unexpectedly, depletion of CD8+ T cells at the time of vaccination or infection also abolished the protective response induced by LACK DNA vaccination, suggesting a role for CD8+ T cells in DNA vaccine induced protection to L. major. Thus, DNA immunization may offer an attractive alternative vaccination strategy against intracellular pathogens, as compared with conventional vaccination with antigens combined with adjuvants.

scholarly journals Granulocyte-Macrophage Colony-Stimulating Factor-Deficient Mice Have Impaired Resistance to Blood-Stage Malaria

2001 ◽  
Vol 69 (1) ◽  
pp. 129-136 ◽  
Author(s):  
Julie Riopel ◽  
MiFong Tam ◽  
Karkada Mohan ◽  
Michael W. Marino ◽  
Mary M. Stevenson
Keyword(s):  
Blood Stage ◽  
Colony Stimulating Factor ◽  
Necrosis Factor Alpha ◽  
Gm Csf ◽  
Tnf Α ◽  
Macrophage Colony Stimulating Factor ◽  
Ifn Γ ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Blood Stage Malaria

ABSTRACT The contribution of granulocyte-macrophage colony-stimulating factor (GM-CSF), a hematopoietic and immunoregulatory cytokine, to resistance to blood-stage malaria was investigated by infecting GM-CSF-deficient (knockout [KO]) mice with Plasmodium chabaudi AS. KO mice were more susceptible to infection than wild-type (WT) mice, as evidenced by higher peak parasitemia, recurrent recrudescent parasitemia, and high mortality. P. chabaudiAS-infected KO mice had impaired splenomegaly and lower leukocytosis but equivalent levels of anemia compared to infected WT mice. Both bone marrow and splenic erythropoiesis were normal in infected KO mice. However, granulocyte-macrophage colony formation was significantly decreased in these tissues of uninfected and infected KO mice, and the numbers of macrophages in the spleen and peritoneal cavity were significantly lower than in infected WT mice. Serum levels of gamma interferon (IFN-γ) were found to be significantly higher in uninfected KO mice, and the level of this cytokine was not increased during infection. In contrast, IFN-γ levels were significantly above normal levels in infected WT mice. During infection, tumor necrosis factor alpha (TNF-α) levels were significantly increased in KO mice and were significantly higher than TNF-α levels in infected WT mice. Our results indicate that GM-CSF contributes to resistance to P. chabaudi AS infection and that it is involved in the development of splenomegaly, leukocytosis, and granulocyte-macrophage hematopoiesis. GM-CSF may also regulate IFN-γ and TNF-α production and activity in response to infection. The abnormal responses seen in infected KO mice may be due to the lack of GM-CSF during development, to the lack of GM-CSF in the infected mature mice, or to both.

CD56+ human blood dendritic cells effectively promote TH1-type γδ T-cell responses

Blood ◽  
2009 ◽  
Vol 114 (20) ◽  
pp. 4422-4431 ◽  
Author(s):  
Georg Gruenbacher ◽  
Hubert Gander ◽  
Andrea Rahm ◽  
Walter Nussbaumer ◽  
Nikolaus Romani ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Human Blood ◽  
Γδ T Cells ◽  
Rapid Expansion ◽  
Γδ T Cell ◽  
Hla Dr ◽  
Tnf Α ◽  
Ifn Γ

Abstract CD56+ human dendritic cells (DCs) have recently been shown to differentiate from monocytes in response to GM-CSF and type 1 interferon in vitro. We show here that CD56+ cells freshly isolated from human peripheral blood contain a substantial subset of CD14+CD86+HLA-DR+ cells, which have the appearance of intermediate-sized lymphocytes but spontaneously differentiate into enlarged DC-like cells with substantially increased HLA-DR and CD86 expression or into fully mature CD83+ DCs in response to appropriate cytokines. Stimulation of CD56+ cells containing both DCs and abundant γδ T cells with zoledronate and interleukin-2 (IL-2) resulted in the rapid expansion of γδ T cells as well as in IFN-γ, TNF-α, and IL-1β but not in IL-4, IL-10, or IL-17 production. IFN-γ, TNF-α, and IL-1β production were almost completely abolished by depleting CD14+ cells from the CD56+ subset before stimulation. Likewise, depletion of CD14+ cells dramatically impaired γδ T-cell expansion. IFN-γ production could also be blocked by neutralizing the effects of endogenous IL-1β and TNF-α. Conversely, addition of recombinant IL-1β, TNF-α, or both further enhanced IFN-γ production and strongly up-regulated IL-6 production. Our data indicate that CD56+ DCs from human blood are capable of stimulating CD56+ γδ T cells, which may be harnessed for immunotherapy.

scholarly journals Bovine Immune Response to Vaccination and Infection with Leptospira borgpetersenii Serovar Hardjo

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Jennifer H. Wilson-Welder ◽  
David P. Alt ◽  
Jarlath E. Nally ◽  
Steven C. Olsen
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Lymph Nodes ◽  
Γδ T Cells ◽  
Regional Lymph Nodes ◽  
Content Type ◽  
Oil Emulsion ◽  
Leptospira Borgpetersenii ◽  
Ifn Γ ◽  
Experimental Challenge

ABSTRACT This study examined the humoral and cellular response of cattle vaccinated with two commercial leptospiral vaccines, Leptavoid and Spirovac, and a novel bacterin vaccine using Seppic Montanide oil emulsion adjuvant. Vaccination was followed by experimental challenge. All vaccinated cattle were protected from colonization of the kidney and shedding of Leptospira in urine, as detected by culture and immunofluorescence assay. Agglutinating antibody titers were detected in vaccinated cattle at 4 weeks following vaccination, with small anamnestic response detected following experimental challenge. Only animals vaccinated with the oil emulsion-adjuvanted bacterin produced significant IgG2 titers following vaccination, and nonvaccinated animals produced serum IgA titers after experimental challenge. CD4+ and γδ T cells from vaccinated cattle proliferated when cultured with antigen ex vivo. Cellular responses included a marked proliferation of γδ T cells immediately following experimental challenge in vaccinated cattle and release of gamma interferon (IFN-γ), interleukin 17a (IL-17a), and IL-12p40 from stimulated cells. Proliferative and cytokine responses were found not just in peripheral mononuclear cells but also in lymphocytes isolated from renal lymph nodes at 10 weeks following experimental challenge. Overall, effects of leptospirosis vaccination and infection were subtle, resulting in only modest activation of CD4+ and γδ T cells. The use of Seppic Montanide oil emulsion adjuvants may shorten the initiation of response to vaccination, which could be useful during outbreaks or in areas where leptospirosis is endemic. IMPORTANCE Leptospirosis is an underdiagnosed, underreported zoonotic disease of which domestic livestock can be carriers. As a reservoir host for Leptospira borgpetersenii serovar Hardjo, cattle may present with reproductive issues, including abortion, birth of weak or infected calves, or failure to breed. Despite years of study and the availability of commercial vaccines, detailed analysis of the bovine immune response to vaccination and Leptospira challenge is lacking. This study evaluated immunologic responses to two efficacious commercial vaccines and a novel bacterin vaccine using an adjuvant chosen for enhanced cellular immune responses. Antigen-specific responsive CD4 and γδ T cells were detected following vaccination and were associated with release of inflammatory cytokines IFN-γ and IL-17a after stimulation. CD4 and γδ cells increased in the first week after infection and, combined with serum antibody, may play a role in clearance of bacteria from the blood and resident tissues. Additionally, these antigen-reactive T cells were found in the regional lymph nodes following infection, indicating that memory responses may not be circulating but are still present in regional lymph nodes. The information gained in this study expands knowledge of bovine immune response to leptospirosis vaccines and infection. The use of oil emulsion adjuvants may enhance early immune responses to leptospiral bacterins, which could be useful in outbreaks or situations where leptospirosis is endemic.

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