scholarly journals Persistent Antigen Presentation after Acute Vesicular Stomatitis Virus Infection

2006 ◽  
Vol 81 (4) ◽  
pp. 2039-2046 ◽  
Author(s):  
Damian L. Turner ◽  
Linda S. Cauley ◽  
Kamal M. Khanna ◽  
Leo Lefrançois
Keyword(s):  
T Cells ◽  
T Cell ◽  
Virus Infection ◽  
Antigen Presentation ◽  
Vesicular Stomatitis Virus ◽  
Cd8 T Cells ◽  
Antigen Expression ◽  
T Cell Response ◽  
Antiviral Immune Response ◽  
Vesicular Stomatitis

ABSTRACT Long-term antigen expression is believed to play an important role in modulation of T-cell responses to chronic virus infections. However, recent studies suggest that immune responses may occur late after apparently acute infections. We have now analyzed the CD8 T-cell response to vesicular stomatitis virus (VSV), which is thought to cause to an infection characterized by rapid virus clearance by innate and adaptive immune system components. Unexpectedly, virus-encoded antigen was detectable more than 6 weeks after intranasal VSV infection in both draining and nondraining lymph nodes by adoptively transferred CD8 T cells. Infection with Listeria monocytogenes expressing the same antigen did not result in prolonged antigen presentation. Weeks after VSV infection, discrete T-cell clustering with dendritic cells within the lymph node was observed after transfer of antigen-specific CD8 T cells. Moreover, memory CD8 T cells as defined by phenotype and function were generated from naïve CD8 T cells entering the response late after infection. These findings suggested that protracted antigen presentation after an apparently acute virus infection may contribute to an ongoing antiviral immune response.

scholarly journals Differential Antigen Presentation Regulates the Changing Patterns of CD8+ T Cell Immunodominance in Primary and Secondary Influenza Virus Infections

2003 ◽  
Vol 198 (3) ◽  
pp. 399-410 ◽  
Author(s):  
Sherry R. Crowe ◽  
Stephen J. Turner ◽  
Shannon C. Miller ◽  
Alan D. Roberts ◽  
Rachel A. Rappolo ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Virus Infection ◽  
Antigen Presentation ◽  
Cd8 T Cells ◽  
Cell Response ◽  
Influenza Virus Infection ◽  
Cd8 T Cell ◽  
T Cell Response

The specificity of CD8+ T cell responses can vary dramatically between primary and secondary infections. For example, NP366–374/Db- and PA224–233/Db-specific CD8+ T cells respond in approximately equal numbers to a primary influenza virus infection in C57BL/6 mice, whereas NP366–374/Db-specific CD8+ T cells dominate the secondary response. To investigate the mechanisms underlying this changing pattern of immunodominance, we analyzed the role of antigen presentation in regulating the specificity of the T cell response. The data show that both dendritic and nondendritic cells are able to present the NP366–374/Db epitope, whereas only dendritic cells effectively present the PA224–233/Db epitope after influenza virus infection, both in vitro and in vivo. This difference in epitope expression favored the activation and expansion of NP366–374/Db-specific CD8+ memory T cells during secondary infection. The data also show that the immune response to influenza virus infection may involve T cells specific for epitopes, such as PA224–233/Db, that are poorly expressed at the site of infection. In this regard, vaccination with the PA224–233 peptide actually had a detrimental effect on the clearance of a subsequent influenza virus infection. Thus, differential antigen presentation impacts both the specificity of the T cell response and the efficacy of peptide-based vaccination strategies.

scholarly journals Mechanisms that allow vaccination against an oncolytic vesicular stomatitis virus-encoded transgene to enhance safety without abrogating oncolysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Amanda W. K. AuYeung ◽  
Robert C. Mould ◽  
Ashley A. Stegelmeier ◽  
Jacob P. van Vloten ◽  
Khalil Karimi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Vesicular Stomatitis Virus ◽  
Cell Response ◽  
Viral Infections ◽  
T Cell Response ◽  
Oncolytic Viruses ◽  
Oncolytic Virotherapy ◽  
Cell Immunity ◽  
Vesicular Stomatitis

AbstractVaccination can prevent viral infections via virus-specific T cells, among other mechanisms. A goal of oncolytic virotherapy is replication of oncolytic viruses (OVs) in tumors, so pre-existing T cell immunity against an OV-encoded transgene would seem counterproductive. We developed a treatment for melanomas by pre-vaccinating against an oncolytic vesicular stomatitis virus (VSV)-encoded tumor antigen. Surprisingly, when the VSV-vectored booster vaccine was administered at the peak of the primary effector T cell response, oncolysis was not abrogated. We sought to determine how oncolysis was retained during a robust T cell response against the VSV-encoded transgene product. A murine melanoma model was used to identify two mechanisms that enable this phenomenon. First, tumor-infiltrating T cells had reduced cytopathic potential due to immunosuppression. Second, virus-induced lymphopenia acutely removed virus-specific T cells from tumors. These mechanisms provide a window of opportunity for replication of oncolytic VSV and rationale for a paradigm change in oncolytic virotherapy, whereby immune responses could be intentionally induced against a VSV-encoded melanoma-associated antigen to improve safety without abrogating oncolysis.

scholarly journals Measles Virus-Specific CD4 T-Cell Activity Does Not Correlate with Protection against Lung Infection or Viral Clearance

2007 ◽  
Vol 81 (16) ◽  
pp. 8571-8578 ◽  
Author(s):  
Karen Pueschel ◽  
Annette Tietz ◽  
Mary Carsillo ◽  
Michael Steward ◽  
Stefan Niewiesk
Keyword(s):  
T Cells ◽  
T Cell ◽  
Virus Infection ◽  
Cd8 T Cells ◽  
Cell Response ◽  
Cd4 T Cells ◽  
Neutralizing Antibodies ◽  
Measles Virus ◽  
T Cell Response ◽  
Cd4 T Cell

ABSTRACT Acute measles in children can be prevented by immunization with the live attenuated measles vaccine virus. Although immunization is able to induce CD4 and CD8 T cells as well as neutralizing antibodies, only the latter have been correlated with protective immunity. CD8 T cells, however, have been documented to be important in viral clearance in the respiratory tract, whereas CD4 T cells have been shown to be protective in a mouse encephalitis model. In order to investigate the CD4 T-cell response in infection of the respiratory tract, we have defined a T-cell epitope in the hemagglutinin (H) protein for immunization and developed a monoclonal antibody for depletion of CD4 T cells in the cotton rat model. Although the kinetics of CD4 T-cell development correlated with clearance of virus, the depletion of CD4 T cells during the primary infection did not influence viral titers in lung tissue. Immunization with the H epitope induced a CD4 T-cell response but did not protect against infection. Immunization in the presence of maternal antibodies resulted in the development of a CD4 T-cell response which (in the absence of neutralizing antibodies) did not protect against infection. In summary, CD4 T cells do not seem to protect against infection after immunization and do not participate in clearance of virus infection from lung tissue during measles virus infection. We speculate that the major role of CD4 T cells is to control and clear virus infection from other affected organs like the brain.

scholarly journals Agonistic Anti-CD40 Enhances the CD8+ T Cell Response during Vesicular Stomatitis Virus Infection

PLoS ONE ◽  
2014 ◽  
Vol 9 (8) ◽  
pp. e106060 ◽  
Author(s):  
Julianne M. Zickovich ◽  
Susan I. Meyer ◽  
Hideo Yagita ◽  
Joshua J. Obar
Keyword(s):  
T Cell ◽  
Virus Infection ◽  
Vesicular Stomatitis Virus ◽  
Cell Response ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Vesicular Stomatitis

scholarly journals Type I Interferons Regulate the Magnitude and Functionality of Mouse Polyomavirus-Specific CD8 T Cells in a Virus Strain-Dependent Manner

2016 ◽  
Vol 90 (10) ◽  
pp. 5187-5199 ◽  
Author(s):  
Qingsong Qin ◽  
Shwetank ◽  
Elizabeth L. Frost ◽  
Saumya Maru ◽  
Aron E. Lukacher
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Response ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Single Amino Acid ◽  
Type I ◽  
Type I Ifns ◽  
Vp1 Capsid Protein

ABSTRACTMouse polyomavirus (MPyV) is a ubiquitous persistent natural mouse pathogen. A glutamic acid (E)-to-glycine (G) difference at position 91 of the VP1 capsid protein shifts the profile of tumors induced by MPyV from an epithelial to a mesenchymal cell origin. Here we asked if this tropism difference affects the MPyV-specific CD8 T cell response, which controls MPyV infection and tumorigenesis. Infection by the laboratory MPyV strain RA (VP1-91G) or a strain A2 mutant with an E-to-G substitution at VP1 residue 91 [A2(91G)] generated a markedly smaller virus-specific CD8 T cell response than that induced by A2(VP1-91E) infection. Mutant A2(91G)-infected mice showed a higher frequency of memory precursor (CD127hiKLRG1lo) CD8 T cells and a higher recall response than those of A2-infected mice. Using T cell receptor (TCR)-transgenic CD8 T cells and immunization with peptide-pulsed dendritic cells, we found that early bystander inflammation associated with A2 infection contributed to recruitment of the larger MPyV-specific CD8 T cell response. Beta interferon (IFN-β) transcripts were induced early during A2 or A2(91G) infections. IFN-β inhibited replication of A2 and A2(91G)in vitro. Using mice lacking IFN-αβ receptors (IFNAR−/−), we showed that type I IFNs played a role in controlling MPyV replicationin vivobut differentially affected the magnitude and functionality of virus-specific CD8 T cells recruited by A2 and A2(91G) viral infections. These data indicate that type I IFNs are involved in protection against MPyV infection and that their effect on the antiviral CD8 T cell response depends on capsid-mediated tropism properties of the MPyV strain.IMPORTANCEIsolates of the human polyomavirus JC virus from patients with the frequently fatal demyelinating brain disease progressive multifocal leukoencephalopathy (PML) carry single amino acid substitutions in the domain of the VP1 capsid protein that binds the sialic acid moiety of glycoprotein/glycolipid receptors on host cells. These VP1 mutations may alter neural cell tropism or enable escape from neutralizing antibodies. Changes in host cell tropism can affect recruitment of virus-specific CD8 T cells. Using mouse polyomavirus, we demonstrate that a single amino acid difference in VP1 known to shift viral tropism profoundly affects the quantity and quality of the anti-polyomavirus CD8 T cell response and its differentiation into memory cells. These findings raise the possibility that CD8 T cell responses to infections by human polyomaviruses may be influenced by VP1 mutations involving domains that engage host cell receptors.

scholarly journals Role of Thymic Output in Regulating CD8 T-Cell Homeostasis during Acute and Chronic Viral Infection

2005 ◽  
Vol 79 (15) ◽  
pp. 9419-9429 ◽  
Author(s):  
Nicole E. Miller ◽  
Jennifer R. Bonczyk ◽  
Yumi Nakayama ◽  
M. Suresh
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Response ◽  
Viral Infections ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Cell Responses ◽  
Lcmv Infection

ABSTRACT Although it is well documented that CD8 T cells play a critical role in controlling chronic viral infections, the mechanisms underlying the regulation of CD8 T-cell responses are not well understood. Using the mouse model of an acute and chronic lymphocytic choriomeningitis virus (LCMV) infection, we have examined the relative importance of peripheral T cells and thymic emigrants in the elicitation and maintenance of CD8 T-cell responses. Virus-specific CD8 T-cell responses were compared between mice that were either sham thymectomized or thymectomized (Thx) at ∼6 weeks of age. In an acute LCMV infection, thymic deficiency did not affect either the primary expansion of CD8 T cells or the proliferative renewal and maintenance of virus-specific lymphoid and nonlymphoid memory CD8 T cells. Following a chronic LCMV infection, in Thx mice, although the initial expansion of CD8 T cells was normal, the contraction phase of the CD8 T-cell response was exaggerated, which led to a transient but striking CD8 T-cell deficit on day 30 postinfection. However, the virus-specific CD8 T-cell response in Thx mice rebounded quickly and was maintained at normal levels thereafter, which indicated that the peripheral T-cell repertoire is quite robust and capable of sustaining an effective CD8 T-cell response in the absence of thymic output during a chronic LCMV infection. Taken together, these findings should further our understanding of the regulation of CD8 T-cell homeostasis in acute and chronic viral infections and might have implications in the development of immunotherapy.

scholarly journals Contribution of Herpesvirus Specific CD8 T Cells to Anti-Viral T Cell Response in Humans

2010 ◽  
Vol 6 (8) ◽  
pp. e1001051 ◽  
Author(s):  
Elena Sandalova ◽  
Diletta Laccabue ◽  
Carolina Boni ◽  
Anthony T. Tan ◽  
Katja Fink ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Response ◽  
T Cell Response

scholarly journals CD4+CD8+T Cells Represent a Significant Portion of the Anti-HIV T Cell Response to Acute HIV Infection

2012 ◽  
Vol 188 (9) ◽  
pp. 4289-4296 ◽  
Author(s):  
Marc A. Frahm ◽  
Ralph A. Picking ◽  
JoAnn D. Kuruc ◽  
Kara S. McGee ◽  
Cynthia L. Gay ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Cd8 T Cells ◽  
Cell Response ◽  
T Cell Response ◽  
Acute Hiv Infection ◽  
Acute Hiv ◽  
Anti Hiv

scholarly journals 596 Combining Bempegaldesleukin (CD122-preferential IL-2 pathway agonist) and NKTR-262 (TLR7/8 agonist) pairs local innate activation with systemic CD8+ T cell expansion to enhance anti-tumor immunity

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A626-A626
Author(s):  
Annah Rolig ◽  
Daniel Rose ◽  
Grace Helen McGee ◽  
Saul Kivimae ◽  
Werner Rubas ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Cycle Phase ◽  
Tumor Cell Death ◽  
Specific Immunity

BackgroundTumor cell death caused by radiation therapy (RT) can trigger anti-tumor immune responses in part because dying cells release adjuvant factors that amplify and sustain DC and T cell responses. We previously demonstrated that bempegaldesleukin (BEMPEG:NKTR-214, a first-in-class CD122-preferential IL-2 pathway agonist), significantly enhanced the anti-tumor efficacy of RT through a T cell-dependent mechanism. Because RT can induce either immunogenic or tolerogenic cell death, depending on a multitude of factors (radiation dose, cell cycle phase, and tumor microenvironment), we hypothesized that providing a specific immunogenic adjuvant, like intratumoral NKTR-262, a novel toll-like receptor (TLR) 7/8 agonist, to the tumor site would further improve systemic tumor-specific immunity by promoting synergistic activation of local immunostimulatory innate immune responses. Therefore, we evaluated whether intratumoral NKTR-262, combined with systemic BEMPEG treatment would result in improved tumor-specific immunity and survival compared to BEMPEG combined with RT.MethodsTumor-bearing mice (CT26; EMT6) received BEMPEG (0.8 mg/kg; iv), RT (16 Gy x 1), and/or intratumoral NKTR-262 (0.5 mg/kg). Flow cytometry was used to evaluate CD4+ and CD8+ T cell activation status in the blood and tumor (7 days post-treatment). The contribution of specific immune subsets was determined by depletion of CD4+, CD8+, or NK cells. CD8+ T cell cytolytic activity was determined in vitro with an Incucyte assay. Data are representative of 1–2 independent experiments (n=5–14/group) and statistical significance was determined by 1-way ANOVA (p-value cut-off of 0.05).ResultsBEMPEG/NKTR-262 resulted in significantly improved survival compared to BEMPEG/RT. Both combination therapies were CD8+ T cell dependent. However, response to BEMPEG/NKTR-262 was characterized by a significant expansion of activated CD8+ T cells (GzmA+; Ki-67+; ICOS+; PD-1+) in the blood, which correlated with reduced tumor size (p<0.05). In the tumor, BEMPEG/NKTR-262 induced higher frequencies of GzmA+ CD8+ T cells exhibiting reduced expression of suppressive molecules (PD-1+, TIM-3+), compared to BEMPEG/RT. Additionally, CD8+ T cells isolated from BEMPEG/NKTR-262-treated tumors had greater cytolytic capacity than those from BEMPEG/RT-treated mice.ConclusionsCombining BEMPEG with NKTR-262 lead to a more robust expansion of activated CD8+ T cells compared to the BEMPEG/RT combination. Enhancement of the activated CD8+ T cell response in mice treated with NKTR-262 in combination with BEMPEG suggests that intratumoral TLR stimulation provides superior antigen presentation and costimulatory activity compared to RT. A clinical trial of BEMPEG/NKTR-262 for patients with metastatic solid tumors is in progress (NCT03435640).

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