scholarly journals T-Cell Hyporesponsiveness Induced by Activated Macrophages through Nitric Oxide Production in Mice Infected withMycobacterium tuberculosis

1999 ◽  
Vol 67 (7) ◽  
pp. 3221-3226 ◽  
Author(s):  
Shigeki Nabeshima ◽  
Mari Nomoto ◽  
Goro Matsuzaki ◽  
Kenji Kishihara ◽  
Hatsumi Taniguchi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Cell Response ◽  
Cd4 T Cells ◽  
Proliferative Response ◽  
Transforming Growth Factor ◽  
T Cell Response ◽  
Activated Macrophages

ABSTRACT In active tuberculosis, T-cell response to Mycobacterium tuberculosis is known to be reduced. In the course ofMycobacterium tuberculosis infection in mice, we observed that T-cell proliferation in response to M. tuberculosispurified protein derivative (PPD) reached the maximum level on day 7, then declined to the minimal level on day 14, and persisted at a low level through day 28 postinfection. The frequency of PPD-specific CD4 T cells in the spleen on day 28 decreased to one-sixth on day 7. To further investigate the mechanism of this T-cell hyporesponsiveness, we next analyzed the suppressive activity of spleen macrophages on T-cell function. The nonspecific proliferative response of naive T cells and the PPD-specific proliferative response of T cells were suppressed by day 28 macrophages, but not by day 7 macrophages or naive macrophages. This reduction of proliferative response was restored by addition of nitric oxide synthesis inhibitor, NG-monoethyl-l-arginine monoacetate, but not by monoclonal antibody against interleukin 10 or transforming growth factor β. These data indicate that the macrophages from mice chronically infected with M. tuberculosis suppress T-cell response through production of nitric oxide, suggesting that nitric oxide-induced elimination mediated by activated macrophages may reduce the T-cell response and the number of mycobacterium-specific CD4 T cells in vivo.

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.

CD4+ T cells specific for glycoprotein B from cytomegalovirus exhibit extreme conservation of T-cell receptor usage between different individuals

Blood ◽  
2008 ◽  
Vol 111 (4) ◽  
pp. 2053-2061 ◽  
Author(s):  
Laura Crompton ◽  
Naeem Khan ◽  
Rajiv Khanna ◽  
Laxman Nayak ◽  
Paul A. H. Moss
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Response ◽  
Cd4 T Cells ◽  
Clonal Selection ◽  
Cell Receptor ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Extreme Conservation

Antigen-specific CD8+ cytotoxic T cells often demonstrate extreme conservation of T-cell receptor (TCR) usage between different individuals, but similar characteristics have not been documented for CD4+ T cells. CD4+ T cells predominantly have a helper immune role, but a cytotoxic CD4+ T-cell subset has been characterized, and we have studied the cytotoxic CD4+ T-cell response to a peptide from human cytomegalovirus glycoprotein B presented through HLA-DRB*0701. We show that this peptide elicits a cytotoxic CD4+ T-cell response that averages 3.6% of the total CD4+ T-cell repertoire of cytomegalovirus-seropositive donors. Moreover, CD4+ cytotoxic T-cell clones isolated from different individuals exhibit extensive conservation of TCR usage, which indicates strong T-cell clonal selection for peptide recognition. Remarkably, this TCR sequence was recently reported in more than 50% of cases of CD4+ T-cell large granular lymphocytosis. Immunodominance of cytotoxic CD4+ T cells thus parallels that of CD8+ subsets and suggests that cytotoxic effector function is critical to the development of T-cell clonal selection, possibly from immune competition secondary to lysis of antigen-presenting cells. In addition, these TCR sequences are highly homologous to those observed in HLA-DR7+ patients with CD4+ T-cell large granular lymphocytosis and implicate cytomegalovirus as a likely antigenic stimulus for this disorder.

Loss of EBV-Specific CD4+T Cells during Progression to EBV-Related AIDS Non-Hodgkin Lymphoma: Restoration by Highly Active Antiretroviral Therapy (HAART).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3110-3110
Author(s):  
Erwan R. Piriou ◽  
Christine Jansen ◽  
Karel van Dort ◽  
Iris De Cuyper ◽  
Nening M. Nanlohy ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Cd4 T Cells ◽  
Antigen Processing ◽  
Ex Vivo ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Cell Numbers

Abstract Objective: EBV-specific CD8+ T cells have been extensively studied in various settings, and appear to play a major role in the control of EBV-related malignancies. In contrast, it is still unclear whether EBV-specific CD4+ T cells play a role in vivo. To study this question, an assay was developed to measure the CD4+ T-cell response towards two EBV antigens, in both healthy (n=14) and HIV-infected subjects (n=23). In addition, both HAART-treated (n=12) and untreated HIV+ individuals (n=14) - including progressors to EBV-related lymphoma - were studied longitudinally. Methods: EBV-specific CD4+ T cells were stimulated with peptide pools from latent protein EBNA1 and lytic protein BZLF1, and detected by measurement of IFNg-production. Results: After direct ex vivo stimulation, EBNA1 or BZLF1-specific IFNg- (and/or IL2) producing CD4+ T cell numbers were low, and measurable in less than half of the subjects studied (either HIV- and HIV+). Therefore, PBMC were cultured for 12 days in the presence of peptides and IL2 (from day 3), and then restimulated with peptides, allowing specific and reproducible expansion of EBV-specific CD4+ T cells, independent of HLA type and ex vivo antigen processing. Interestingly, numbers of EBV-specific CD4+ T cells inversely correlated with EBV viral load, implying an important role for EBV-specific CD4+ T cells in the control of EBV in vivo. Untreated HIV-infected individuals had a lower CD4+ T cell response to EBNA1 and BZLF1 as compared to healthy EBV carriers and HAART-treated HIV+ subjects. In longitudinal samples, EBNA1-specific, but not BZLF1-specific T-cell numbers increased after HAART, while EBV load was not affected by treatment. In all the progressors to EBV-related lymphoma, EBV-specific CD4+ T cells were lost at least 24 months before lymphoma diagnosis. Conclusions: Both cross-sectional and longitudinal data suggest an important role for EBV-specific CD4+ T cells in the control of EBV-related malignancies. Furthermore, it seems that HAART treatment leads to recovery of EBNA1-specific, but not BZLF1-specific CD4+ T-cell responses, implying changes in the latency pattern of EBV, despite an unaltered cell-associated EBV DNA load. Thus, early HAART treatment might prevent loss of specific CD4+ T-cell help and progression to NHL.

scholarly journals Deciphering the Plasmodium falciparum malaria-specific CD4+ T cell response: ex vivo detection of high frequencies of PD-1+TIGIT+ EXP1-specific CD4+ T cells using a novel HLA-DR11-restricted MHC class II tetramer

2021 ◽  
Author(s):  
Sophia Schulte ◽  
Janna Heide ◽  
Christin Ackermann ◽  
Sven Peine ◽  
Michael Ramharter ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Cell Response ◽  
Cd4 T Cells ◽  
Ex Vivo ◽  
Class Ii ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Inhibitory Receptors

Abstract Relatively little is known about the ex vivo frequency and phenotype of the P. falciparum-specific CD4+ T cell response in humans. The exported protein 1 (EXP1) is expressed by plasmodia at both, the liver stage and blood stage, of infection making it a potential target for CD4+ and CD8+ effector T cells. Here, a fluorochrome-labelled HLA-DRB1*11:01-restriced MHC class II tetramer derived from the P. falciparum EXP1 (aa62-74) was established for ex vivo tetramer analysis and magnetic bead enrichment in ten patients with acute malaria. EXP1-specific CD4+ T cells were detectable in nine out of ten (90%) malaria patients expressing the HLA-DRB1*11 molecule with an average ex vivo frequency of 0.11% (0-0.22%) of total CD4+ T cells. The phenotype of EXP1-specific CD4+ T cells was further assessed using co-staining with activation (CD38, HLA-DR, CD26), differentiation (CD45RO, CCR7, KLRG1, CD127), senescence (CD57) and co-inhibitory (PD-1, TIGIT, LAG-3, TIM-3) markers as well as the ectonucleotidases CD39 and CD73. EXP1-specific tetramer+ CD4+ T cells had a distinct phenotype compared to bulk CD4+ T cells and displayed a highly activated effector memory phenotype with elevated levels of co-inhibitory receptors and activation markers: EXP1-specific CD4+ T cells universally expressed the co-inhibitory receptors PD-1 and TIGIT as well as the activation marker CD38 and showed elevated frequencies of CD39. These results demonstrate that MHC class II tetramer enrichment is a sensitive approach to investigate ex vivo antigen-specific CD4+ T cells in malaria patients that will aid further analysis of the role of CD4+ T cells during malaria.

scholarly journals Novel method for detection of virus-specific CD4+ T?cells indicates a decreased EBV-specific CD4+ T?cell response in untreated HIV-infected subjects

2005 ◽  
Vol 35 (3) ◽  
pp. 796-805 ◽  
Author(s):  
Erwan?R. Piriou ◽  
Karel van Dort ◽  
Nening?M. Nanlohy ◽  
Marinus?H. van Oers ◽  
Frank Miedema ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Cd4 T Cells ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Novel Method

scholarly journals Induction of a virus-specific effector–memory CD4+ T cell response by attenuated SIV infection

2006 ◽  
Vol 203 (12) ◽  
pp. 2661-2672 ◽  
Author(s):  
Marie-Claire Gauduin ◽  
Yi Yu ◽  
Amy Barabasz ◽  
Angela Carville ◽  
Mike Piatak ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
High Frequency ◽  
Cd4 T Cells ◽  
Rhesus Macaques ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Effector Memory ◽  
Specific Effector

We investigated simian immunodeficiency virus (SIV)-specific CD4+ T cell responses in rhesus macaques chronically infected with attenuated or pathogenic SIV strains. Analysis of SIVΔnef-infected animals revealed a relatively high frequency of SIV-specific CD4+ T cells representing 4–10% of all CD4+ T lymphocytes directed against multiple SIV proteins. Gag-specific CD4+ T cells in wild-type SIV-infected animals were 5–10-fold lower in frequency and inversely correlated with the level of plasma viremia. SIV-specific CD4+ cells from SIVΔnef animals were predominantly CD27−CD28−CD45RAlowCCR7−CCR5−, consistent with an effector–memory subset, and included a fully differentiated CD45RA+CCR7− subpopulation. In contrast, SIV-specific CD4+ T cells from SIV-infected animals were mostly CD27+CD28+CD45RA−CCR7+CCR5+, consistent with an early central memory phenotype. The CD45RA+CCR7−CD4+ subset from SIVΔnef animals was highly enriched for effector CD4+ T cells, as indicated by the perforin expression and up-regulation of the lysosomal membrane protein CD107a after SIV Gag stimulation. SIV-specific CD4+ T cells in attenuated SIV-infected animals were increased in frequency in bronchioalveolar lavage and decreased in lymph nodes, consistent with an effector–memory T cell population. The ability of SIVΔnef to induce a high frequency virus-specific CD4+ T cell response with direct effector function may play a key role in protective immunity produced by vaccination with attenuated SIV strains.

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.

Sign in / Sign up

Export Citation Format

Share Document