scholarly journals Dietary fish oil alters the accumulation of antigen‐specific CD4 + T cells in the lymph nodes of recipient mice following adoptive transfer and immunization

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Wooki Kim ◽  
Ping Zhang ◽  
Roger Smith ◽  
David N. McMurray ◽  
Robert S. Chapkin
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Fish Oil ◽  
Adoptive Transfer ◽  
Cd4 T Cells ◽  
Dietary Fish

scholarly journals Stem Cell-Derived Viral Antigen-Specific T Cells Suppress HIV Replication and PD-1 Expression on CD4+ T Cells

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 753
Author(s):  
Mohammad Haque ◽  
Fengyang Lei ◽  
Xiaofang Xiong ◽  
Yijie Ren ◽  
Hao-Yun Peng ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Adoptive Transfer ◽  
Cd4 T Cells ◽  
Viral Antigen ◽  
Peritoneal Macrophages ◽  
Hiv Replication ◽  
Specific Ctls ◽  
Immunodeficiency Virus ◽  
Hiv 1

The viral antigen (Ag)-specific CD8+ cytotoxic T lymphocytes (CTLs) derived from pluripotent stem cells (PSCs), i.e., PSC-CTLs, have the ability to suppress the human immunodeficiency virus (HIV) infection. After adoptive transfer, PSC-CTLs can infiltrate into the local tissues to suppress HIV replication. Nevertheless, the mechanisms by which the viral Ag-specific PSC-CTLs elicit the antiviral response remain to be fully elucidated. In this study, we generated the functional HIV-1 Gag epitope SL9-specific CTLs from the induced PSC (iPSCs), i.e., iPSC-CTLs, and investigated the suppression of SL9-specific iPSC-CTLs on viral replication and the protection of CD4+ T cells. A chimeric HIV-1, i.e., EcoHIV, was used to produce HIV replication in mice. We show that adoptive transfer of SL9-specific iPSC-CTLs greatly suppressed EcoHIV replication in the peritoneal macrophages and spleen in the animal model. Furthermore, we demonstrate that the adoptive transfer significantly reduced expression of PD-1 on CD4+ T cells in the spleen and generated persistent anti-HIV memory T cells. These results indicate that stem cell-derived viral Ag-specific CTLs can robustly accumulate in the local tissues to suppress HIV replication and prevent CD4+ T cell exhaustion through reduction of PD-1 expression.

scholarly journals Mucosal immune stimulation with HSV-2 and polyICLC boosts control of viremia in SIVΔNef vaccinated rhesus macaques with breakthrough SIV infection

2020 ◽  
Author(s):  
Meropi Aravantinou ◽  
Olga Mizenina ◽  
Thilo Brill ◽  
Jessica Kenney ◽  
Christine Timmons ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Immune Activation ◽  
Vaccine Efficacy ◽  
Cd4 T Cells ◽  
Hiv Vaccine ◽  
Live Attenuated Vaccine ◽  
Siv Infection ◽  
The Impact

ABSTRACTDevelopment of an effective human immunodeficiency virus (HIV) vaccine is among the highest priorities in the biomedical research agenda. Adjuvants enhance vaccine efficacy, but in the case of HIV, strong or inappropriate immune activation may undermine protection by increasing HIV susceptibility. Co-infection with immunomodulatory pathogens may also impact vaccine efficacy. In the rhesus macaque rectal SIVΔNef live attenuated vaccine model, we utilized a low virulence HSV-2 infection and the double-stranded RNA viral mimic polyICLC as tools to probe the effects of distinct types of immune activation on HIV vaccine efficacy and explore novel correlates of protection from wild type SIV. Rectally administered HSV-2 and polyICLC impacted the protection conferred by mucosal SIVΔNef vaccination by favoring partial protection in animals with breakthrough infection following virulent SIV challenge (“Controllers”). However, SIVΔNef persistence in blood and tissues did not predict protection in this rectal immunization and challenge model. Non-controllers had similar SIVΔNef viremia as completely protected macaques, and while they tended to have less replication competent SIVΔNef in lymph nodes, controllers had no recoverable virus in the lymph nodes. Non-controllers differed from protected macaques immunologically by having a greater frequency of pro-inflammatory CXCR3+CCR6+ CD4 T cells in blood and a monofunctional IFNγ-dominant CD8 T cell response in lymph nodes. Controller phenotype was associated with heightened IFNα production during acute SIV infection and a greater frequency of CXCR5+ CD4 T cells in blood pre-challenge despite a lower frequency of cells with the T follicular helper (Tfh) cell phenotype in blood and lymph nodes. Our results establish novel correlates of immunological control of SIV infection while reinforcing the potential importance of T cell functionality and location in SIVΔNef efficacy. Moreover, this work highlights that triggering of mucosal immunity can aid mucosal vaccine strategies rather than undermine protection.AUTHOR SUMMARYAn efficacious HIV vaccine is essential to contain the HIV pandemic. Vaccine-mediated protection from HIV may be either enhanced or obstructed by mucosal immune activation; thus, the impact of adjuvants and underlying co-infections that lead to immune activation needs to be evaluated. Using the SIV macaque model, we set out to study the impact of underlying infection with HSV-2 or treatment with the adjuvant polyICLC on rectal immunization with the live attenuated vaccine SIVΔNef. We found that neither stimulus impacted complete protection from SIV; however, the combination of HSV-2 and polyICLC improved control of infection in animals that were not completely protected. Compared with non-controller macaques, controllers had less inflammatory T cells before SIV challenge as well as greater gene expression of IFNα and more functional SIV-specific T cells after infection. The results add to our understanding of the mechanisms of SIVΔNef protection and demonstrate that mucosal immune activation does not necessarily undermine protection in mucosal vaccination against HIV.

scholarly journals Homeostatic Proliferation of Naive CD4+ T Cells in Mesenteric Lymph Nodes Generates Gut-Tropic Th17 Cells

2013 ◽  
Vol 190 (11) ◽  
pp. 5788-5798 ◽  
Author(s):  
Takeshi Kawabe ◽  
Shu-lan Sun ◽  
Tsuyoshi Fujita ◽  
Satoshi Yamaki ◽  
Atsuko Asao ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Cd4 T Cells ◽  
Th17 Cells ◽  
Homeostatic Proliferation ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph

scholarly journals Similar frequency and inducibility of intact HIV-1 proviruses in blood and lymph nodes

2020 ◽  
Author(s):  
Alyssa R Martin ◽  
Alexandra M Bender ◽  
Jada Hackman ◽  
Kyungyoon J Kwon ◽  
Briana A Lynch ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Cd4 T Cells ◽  
Viral Rna ◽  
Latent Reservoir ◽  
Similar Frequency ◽  
Latently Infected ◽  
Infected Cells ◽  
Secondary Lymphoid Organs ◽  
Hiv 1

Abstract Background The HIV-1 latent reservoir (LR) in resting CD4 + T cells is a barrier to cure. LR measurements are commonly performed on blood samples and therefore may miss latently infected cells residing in tissues, including lymph nodes. Methods We determined the frequency of intact HIV-1 proviruses and proviral inducibility in matched peripheral blood (PB) and lymph node (LN) samples from ten HIV-1-infected patients on ART using the intact proviral DNA assay and a novel quantitative viral induction assay. Prominent viral sequences from induced viral RNA were characterized using a next-generation sequencing assay. Results The frequencies of CD4 + T cells with intact proviruses were not significantly different in PB vs LN (61vs104/10 6CD4 + cells), and were substantially lower than frequencies of CD4 + T cells with defective proviruses. The frequencies of CD4 + T cells induced to produce high levels of viral RNA were not significantly different in PB vs LN (4.3/10 6 vs 7.9/10 6), but were 14-fold lower than the frequencies of cells with intact proviruses. Sequencing of HIV-1 RNA from induced proviruses revealed comparable sequences in paired PB and LN samples. Conclusions These results further support the use of PB as an appropriate proxy for the HIV-1 LR in secondary lymphoid organs

scholarly journals Intravenous Arginine Administration Benefits CD4+ T-Cell Homeostasis and Attenuates Liver Inflammation in Mice with Polymicrobial Sepsis

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1047
Author(s):  
Chiu-Li Yeh ◽  
Sharon Angela Tanuseputero ◽  
Jin-Ming Wu ◽  
Yi-Ru Tseng ◽  
Po-Jen Yang ◽  
...  
Keyword(s):  
T Cells ◽  
Single Dose ◽  
Lymph Node ◽  
T Cell ◽  
Lymph Nodes ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Liver Inflammation ◽  
Aortic Lymph Node ◽  
Inos Inhibitor

This study investigated the effects of a single dose of arginine (Arg) administration at the beginning of sepsis on CD4+ T-cell regulation and liver inflammation in C57BL/6J mice. Mice were divided into normal control (NC), sham (SH), sepsis saline (SS), and sepsis Arg (SA) groups. An inducible nitric oxide (NO) synthase (iNOS) inhibitor was administered to additional sepsis groups to evaluate the role of NO during sepsis. Sepsis was induced using cecal ligation and puncture (CLP). The SS and SA groups received saline or Arg (300 mg/kg body weight) via tail vein 1 h after CLP. Mice were euthanized at 12 and 24 h post-CLP. Blood, para-aortic lymph nodes, and liver tissues were collected for further measurement. The findings showed that sepsis resulted in decreases in blood and para-aortic lymph node CD4+ T-cell percentages, whereas percentages of interleukin (IL)-4- and IL-17-expressing CD4+ T cells were upregulated. Compared to the SS group, Arg administration resulted in maintained circulating and para-aortic lymph node CD4+ T cells, an increased Th1/Th2 ratio, and a reduced Th17/Treg ratio post-CLP. In addition, levels of plasma liver injury markers and expression of inflammatory genes in liver decreased. These results suggest that a single dose of Arg administered after CLP increased Arg availability, sustained CD4+ T-cell populations, elicited more-balanced Th1/Th2/Th17/Treg polarization in the circulation and the para-aortic lymph nodes, and attenuated liver inflammation in sepsis. The favorable effects of Arg were abrogated when an iNOS inhibitor was administered, which indicated that NO may be participated in regulating the homeostasis of Th/Treg cells and subsequent liver inflammation during sepsis.

scholarly journals Commensal microbiota drive proliferation of conventional and Foxp3+Regulatory CD4+T cells in mesenteric lymph nodes and Peyer's patches

2013 ◽  
Vol 3 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Sascha Cording ◽  
Diana Fleissner ◽  
Markus M. Heimesaat ◽  
Stefan Bereswill ◽  
Christoph Loddenkemper ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Cd4 T Cells ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Mesenteric Lymph Nodes ◽  
Commensal Microbiota ◽  
Mesenteric Lymph

scholarly journals Functional Tolerance is Maintained Despite Proliferation of CD4 T Cells after Encounter with Tissue-derived Antigen

2002 ◽  
Vol 9 (3) ◽  
pp. 173-176
Author(s):  
Lara J. Ausubel ◽  
Anna Chodos ◽  
Nyree Bekarian ◽  
Abul K. Abbas ◽  
Lucy S. K. Walker
Keyword(s):  
T Cells ◽  
Adoptive Transfer ◽  
Cd4 T Cells ◽  
Negative Selection ◽  
Tissue Injury ◽  
The Self ◽  
Transfer System ◽  
Insulin Promoter ◽  
Functional Tolerance ◽  
Peripheral Activation

Since negative selection in the thymus is incomplete, some self-reactive T cells are able to mature and seed the periphery. To study how these T cells interact following encounter with the self-protein they recognize in the periphery, we have developed an adoptive transfer system in which HEL-specific TCR transgenic CD4 T cells are transferred to mice expressing HEL protein in the pancreas under the control of the rat insulin promoter. Here we show that after adoptive transfer of HEL-specific T cells functional tolerance is maintained despite evidence that the T cells encounter and respond to pancreas-expressed antigen. Even the provision of an additional activation stimulus by peripheral immunization with HEL protein is insufficient to induce the T cells to cause autoimmune tissue injury. However, in the presence of blocking anti-CTLA-4-mAb, immunized adoptive transfer recipients rapidly developed diabetes. These data suggest that the CTLA-4 pathway regulates the pathogenicity of antigen-specific T cells following a peripheral activation stimulus.

8-Methoxypsoralen plus UVA treatment increases the proportion of CLA+ CD25+ CD4+ T cells in lymph nodes of K5.hTGFβ1 transgenic mice

2012 ◽  
Vol 21 (3) ◽  
pp. 228-230 ◽  
Author(s):  
Tej Pratap Singh ◽  
Michael P. Schön ◽  
Katrin Wallbrecht ◽  
Peter Wolf
Keyword(s):  
T Cells ◽  
Transgenic Mice ◽  
Lymph Nodes ◽  
Cd4 T Cells

scholarly journals In Vivo Detection of Dendritic Cell Antigen Presentation to CD4+ T Cells

1997 ◽  
Vol 185 (12) ◽  
pp. 2133-2141 ◽  
Author(s):  
Elizabeth Ingulli ◽  
Anna Mondino ◽  
Alexander Khoruts ◽  
Marc K. Jenkins
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
T Cell Activation ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Delayed Type Hypersensitivity ◽  
Physical Interaction

Although lymphoid dendritic cells (DC) are thought to play an essential role in T cell activation, the initial physical interaction between antigen-bearing DC and antigen-specific T cells has never been directly observed in vivo under conditions where the specificity of the responding T cells for the relevant antigen could be unambiguously assessed. We used confocal microscopy to track the in vivo location of fluorescent dye-labeled DC and naive TCR transgenic CD4+ T cells specific for an OVA peptide–I-Ad complex after adoptive transfer into syngeneic recipients. DC that were not exposed to the OVA peptide, homed to the paracortical regions of the lymph nodes but did not interact with the OVA peptide-specific T cells. In contrast, the OVA peptide-specific T cells formed large clusters around paracortical DC that were pulsed in vitro with the OVA peptide before injection. Interactions were also observed between paracortical DC of the recipient and OVA peptide-specific T cells after administration of intact OVA. Injection of OVA peptide-pulsed DC caused the specific T cells to produce IL-2 in vivo, proliferate, and differentiate into effector cells capable of causing a delayed-type hypersensitivity reaction. Surprisingly, by 48 h after injection, OVA peptide-pulsed, but not unpulsed DC disappeared from the lymph nodes of mice that contained the transferred TCR transgenic population. These results demonstrate that antigen-bearing DC directly interact with naive antigen-specific T cells within the T cell–rich regions of lymph nodes. This interaction results in T cell activation and disappearance of the DC.

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