scholarly journals Cross-Reactive Memory CD4+T Cells Alter the CD8+T-Cell Response to Heterologous Secondary Dengue Virus Infections in Mice in a Sequence-Specific Manner

2009 ◽  
Vol 22 (3) ◽  
pp. 215-219 ◽  
Author(s):  
Coreen M. Beaumier ◽  
Alan L. Rothman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Dengue Virus ◽  
Cell Response ◽  
Cd4 T Cells ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Virus Infections ◽  
Specific Manner ◽  
Memory Cd4 T Cells

MOG extracellular domain (p1–125) triggers elevated frequency of CXCR3+ CD4+ Th1 cells in the CNS of mice and induces greater incidence of severe EAE

2014 ◽  
Vol 20 (10) ◽  
pp. 1312-1321 ◽  
Author(s):  
Jyothi T Mony ◽  
Reza Khorooshi ◽  
Trevor Owens
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Cd4 T Cells ◽  
Cd8 T Cell ◽  
Interferon Γ ◽  
T Cell Response ◽  
Receptor Expression ◽  
Myelin Proteins ◽  
Mhc Ii

Background: Myelin-specific T cells are implicated in multiple sclerosis (MS) and drive experimental autoimmune encephalomyelitis (EAE). EAE is commonly induced with short peptides, whereas in MS, whole myelin proteins are available for immune response. We asked whether immunization with the immunoglobulin-like domain of myelin oligodendrocyte glycoprotein (MOGIgd, residues 1–125) might induce distinct CD4+ T-cell response and/or a stronger CD8+ T-cell response, compared to the 21 amino acid immunodominant MHC II-associating peptide (p35–55). Objectives: Compare both EAE and T-cell responses in C57BL/6 mice immunized with MOGIgd and MOG p35–55. Methods: Cytokine production, and chemokine receptor expression by CD4+ and CD8+ T cells in the mouse central nervous system (CNS), were analyzed by flow cytometry. Results: MOGIgd triggered progression to more severe EAE than MOG p35–55, despite similar time of onset and overall incidence. EAE in MOGIgd-immunized mice was characterized by an increased percentage of CXCR3+ interferon-γ-producing CD4+ T cells in CNS. The CD8+ T-cell response to both immunogens was similar. Conclusions: Increased incidence of severe disease following MOGIgd immunization, accompanied by an increased percentage of CD4+ T cells in the CNS expressing CXCR3 and producing interferon-γ, identifies a pathogenic role for interferon-γ that is not seen when disease is induced with a single Major Histocompatibility Complex (MHC) II-associating epitope.

scholarly journals Chimeric Yellow Fever/Dengue Virus as a Candidate Dengue Vaccine: Quantitation of the Dengue Virus-Specific CD8 T-Cell Response

2000 ◽  
Vol 74 (17) ◽  
pp. 8094-8101 ◽  
Author(s):  
Robbert G. van der Most ◽  
Kaja Murali-Krishna ◽  
Rafi Ahmed ◽  
James H. Strauss
Keyword(s):  
T Cells ◽  
T Cell ◽  
Dengue Virus ◽  
Yellow Fever ◽  
Cd8 T Cells ◽  
Cell Response ◽  
Protective Efficacy ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
E Proteins

ABSTRACT We have constructed a chimeric yellow fever/dengue (YF/DEN) virus, which expresses the premembrane (prM) and envelope (E) genes from DEN type 2 (DEN-2) virus in a YF virus (YFV-17D) genetic background. Immunization of BALB/c mice with this chimeric virus induced a CD8 T-cell response specific for the DEN-2 virus prM and E proteins. This response protected YF/DEN virus-immunized mice against lethal dengue encephalitis. Control mice immunized with the parental YFV-17D were not protected against DEN-2 virus challenge, indicating that protection was mediated by the DEN-2 virus prM- and E-specific immune responses. YF/DEN vaccine-primed CD8 T cells expanded and were efficiently recruited into the central nervous systems of DEN-2 virus challenged mice. At 5 days after challenge, 3 to 4% of CD8 T cells in the spleen were specific for the prM and E proteins, and 34% of CD8 T cells in the central nervous system recognized these proteins. Depletion of either CD4 or CD8 T cells, or both, strongly reduced the protective efficacy of the YF/DEN virus, stressing the key role of the antiviral T-cell response.

scholarly journals Human CD4+ T Cells Displaying Viral Epitopes Elicit a Functional Virus-Specific Memory CD8+ T Cell Response

2007 ◽  
Vol 178 (9) ◽  
pp. 5465-5472 ◽  
Author(s):  
Eleni Adamopoulou ◽  
Jan Diekmann ◽  
Eva Tolosa ◽  
Gaby Kuntz ◽  
Hermann Einsele ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Cd4 T Cells ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Specific Memory ◽  
Memory Cd8 T Cell

scholarly journals CD27 Instructs CD4+ T Cells to Provide Help for the Memory CD8+ T Cell Response after Protein Immunization

2008 ◽  
Vol 181 (2) ◽  
pp. 1071-1082 ◽  
Author(s):  
Yanling Xiao ◽  
Victor Peperzak ◽  
Anna M. Keller ◽  
Jannie Borst
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Cd4 T Cells ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Memory Cd8 T Cell ◽  
Protein Immunization

Primary immune responses to human CMV: a critical role for IFN-γ–producing CD4+ T cells in protection against CMV disease

Blood ◽  
2003 ◽  
Vol 101 (7) ◽  
pp. 2686-2692 ◽  
Author(s):  
Laila E. Gamadia ◽  
Ester B. M. Remmerswaal ◽  
Jan F. Weel ◽  
Frederieke Bemelman ◽  
René A. W. van Lier ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Cd4 T Cells ◽  
Critical Role ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Antibody Responses ◽  
Cd4 T Cell ◽  
Effector Memory

The correlates of protective immunity to disease-inducing viruses in humans remain to be elucidated. We determined the kinetics and characteristics of cytomegalovirus (CMV)–specific CD4+ and CD8+ T cells in the course of primary CMV infection in asymptomatic and symptomatic recipients of renal transplants. Specific CD8+ cytotoxic T lymphocyte (CTL) and antibody responses developed regardless of clinical signs. CD45RA−CD27+CCR7− CTLs, although classified as immature effector cells in HIV infection, were the predominant CD8 effector population in the acute phase of protective immune reactions to CMV and were functionally competent. Whereas in asymptomatic individuals the CMV-specific CD4+ T-cell response preceded CMV-specific CD8+T-cell responses, in symptomatic individuals the CMV-specific effector-memory CD4+ T-cell response was delayed and only detectable after antiviral therapy. The appearance of disease symptoms in these patients suggests that functional CD8+ T-cell and antibody responses are insufficient to control viral replication and that formation of effector-memory CD4+ T cells is necessary for recovery of infection.

scholarly journals Promotion of a Subdominant CD8 T Cell Response during Murine Gammaherpesvirus 68 Infection in the Absence of CD4 T Cell Help

2014 ◽  
Vol 88 (14) ◽  
pp. 7862-7869 ◽  
Author(s):  
Michael L. Freeman ◽  
Alan D. Roberts ◽  
Claire E. Burkum ◽  
David L. Woodland ◽  
Marcia A. Blackman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Cd4 T Cells ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Cd4 T Cell Help ◽  
T Cell Help

ABSTRACTCD8 and CD4 T cells are each critically important for immune control of murine gammaherpesvirus 68 (γHV68) infection. In immunocompetent mice, acute γHV68 infection results in lifelong latency, but in the absence of CD4 T cell help, mice succumb to viral recrudescence and disease. However, the requirements for CD4 T cell help in the generation and maintenance of antiviral CD8 T cell responses are incompletely understood, and it is unclear whether there are epitope-specific differences in the requirement of CD8 T cells for CD4 help. In this report, we characterized the CD8 T cell response to γHV68 in major histocompatibility complex (MHC) class II−/−mice, which lack CD4 T cells, or after antibody-mediated depletion of CD4 T cells. All antiviral CD8 T cells exhibited marked upregulation of surface expression of the inhibitory receptor programmed death-1 (PD-1), but surprisingly, while the immunodominant memory response appeared to be functionally impaired, helpless CD8 T cells of a subdominant specificity had increased numbers and enhanced functionality. Thus, we demonstrate differential requirements for CD4 help in the antiviral CD8 T cell response to a latent gammaherpesvirus.IMPORTANCEγHV68 is a mouse pathogen closely related to the oncogenic human γHVs, which infect a majority of the world's population. Reactivation of these viruses from latency can lead to complications, disease, and even death. CD4 T cells are required for complete immune control of long-term infection, in part by providing key signals to dendritic cells that in turn instruct optimal antiviral CD8 T cell responses. We have investigated multiple virus-specific CD8 T cell responses during infection and identified a subdominant CD8 T cell response that is numerically and functionally enhanced in the absence of CD4 T cell help. This occurs in spite of high surface expression of an inhibitory receptor and in contrast to the immunodominant response, which is impaired. Our data suggest that signals from CD4 T cells are important in maintaining the CD8 T cell hierarchy during γHV infections.

scholarly journals CD4+ T helper cells use CD154–CD40 interactions to counteract T reg cell–mediated suppression of CD8+ T cell responses to influenza

2013 ◽  
Vol 210 (8) ◽  
pp. 1591-1601 ◽  
Author(s):  
André Ballesteros-Tato ◽  
Beatriz León ◽  
Frances E. Lund ◽  
Troy D. Randall
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
T Helper Cells ◽  
Cd4 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
T Helper ◽  
Cell Responses

CD4+ T cells promote CD8+ T cell priming by licensing dendritic cells (DCs) via CD40–CD154 interactions. However, the initial requirement for CD40 signaling may be replaced by the direct activation of DCs by pathogen-derived signals. Nevertheless, CD40–CD154 interactions are often required for optimal CD8+ T cell responses to pathogens for unknown reasons. Here we show that CD40 signaling is required to prevent the premature contraction of the influenza-specific CD8+ T cell response. CD40 is required on DCs but not on B cells or T cells, whereas CD154 is required on CD4+ T cells but not CD8+ T cells, NKT cells, or DCs. Paradoxically, even though CD154-expressing CD4+ T cells are required for robust CD8+ T cell responses, primary CD8+ T cell responses are apparently normal in the absence of CD4+ T cells. We resolved this paradox by showing that the interaction of CD40-bearing DCs with CD154-expressing CD4+ T cells precludes regulatory T cell (T reg cell)–mediated suppression and prevents premature contraction of the influenza-specific CD8+ T cell response. Thus, CD4+ T helper cells are not required for robust CD8+ T cell responses to influenza when T reg cells are absent.

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