The role of antigen presenting cells in the induction of HIV-1 latency in resting CD4+ T-cells

Atherosclerosis is a lipid-driven inflammatory disease characterized by the progressive plaque growth in the vessels. Cytokines are important mediators of inflammation and atherosclerosis. While pro-inflammatory cytokines were extensively investigated, little is known about the role of anti-inflammatory cytokines as to their ability to control vascular inflammation. We tested whether immunoregulatory IL-27R signaling is important to control inflammation in mouse models of atherosclerosis. We found that atherosclerosis-prone mice with hematopoietic deficiency of IL-27R ( Ldlr -/- mice reconstituted with bone marrow from Il27ra -/- ) or global deficiency ( Il27ra -/- x Apoe -/- ) developed significantly larger atherosclerotic lesions compared to controls. Atherosclerotic lesions in IL-27R deficient mice contained more CD45 + leukocytes and CD4 + T cells, which produced pro-atherogenic cytokines IL-17A and TNF-α. These cytokines normally suppressed by IL-27, regulated the expression of CCL2 and other chemokines, which in turn led to accumulation of myeloid CD11b + and CD11c + cells in atherosclerotic aortas. Using two-photon microscopy, we found enhanced interactions between antigen presenting cells and T cells in the aortas of IL-27R deficient mice accompanied by enhanced CD4 T cell proliferation. Moreover, macrophages in Il27ra -/- aortas also demonstrated enhanced ability to produce pro-inflammatory cytokines, including IL-1. The blockade of IL-1R signaling, however, strongly suppressed atherosclerosis progression in IL-27R deficient but not control mice, suggesting an important role of IL-27 in the regulation of IL-1 production in atherosclerosis. Overall, our data demonstrate that IL-27R signaling in atherosclerosis is required to control function of antigen presenting cells modulating subsequent T cell activation in the aortas. Moreover, it controls macrophage activation and pro-inflammatory myeloid cell-derived cytokine production. These mechanisms altogether curb pathogenic T cell lineage differentiation and, thus, atherosclerosis, suggesting potent anti-atherogenic role of IL-27.

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Human antigen presenting cells stimulated with Salmonella delivered influenza antigens induce cytokine production and proliferation of human CD4+ T cells in vitro

Journal of Immunological Methods ◽

10.1016/j.jim.2019.04.006 ◽

2019 ◽

Vol 470 ◽

pp. 20-26

Author(s):

Jehyoung Kim ◽

Irshad Ahmed Hajam ◽

John Hwa Lee

Keyword(s):

T Cells ◽

Cd4 T Cells ◽

Cytokine Production ◽

Antigen Presenting Cells ◽

Antigen Presenting

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Distinct Roles of α7 nAChRs in Antigen-Presenting Cells and CD4+ T Cells in the Regulation of T Cell Differentiation

Frontiers in Immunology ◽

10.3389/fimmu.2019.01102 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 11

Author(s):

Masato Mashimo ◽

Masayo Komori ◽

Yuriko Y. Matsui ◽

Mami X. Murase ◽

Takeshi Fujii ◽

...

Keyword(s):

T Cells ◽

Cell Differentiation ◽

T Cell ◽

Cd4 T Cells ◽

Antigen Presenting Cells ◽

T Cell Differentiation ◽

Antigen Presenting ◽

Α7 Nachrs

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HIV-1TransInfection of CD4+T Cells by Professional Antigen Presenting Cells

Scientifica ◽

10.1155/2013/164203 ◽

2013 ◽

Vol 2013 ◽

pp. 1-30 ◽

Cited By ~ 15

Author(s):

Charles R. Rinaldo

Keyword(s):

T Cells ◽

Virus Replication ◽

Virus Transmission ◽

Antigen Presenting Cells ◽

Activated T Cells ◽

Infection Processes ◽

The Many ◽

Antigen Presenting ◽

Hiv 1 ◽

Virus Subtype

Since the 1990s we have known of the fascinating ability of a complex set of professional antigen presenting cells (APCs; dendritic cells, monocytes/macrophages, and B lymphocytes) to mediate HIV-1transinfection of CD4+T cells. This results in a burst of virus replication in the T cells that is much greater than that resulting from direct,cisinfection of either APC or T cells, ortransinfection between T cells. Such APC-to-T celltransinfection first involves a complex set of virus subtype, attachment, entry, and replication patterns that have many similarities among APC, as well as distinct differences related to virus receptors, intracellular trafficking, and productive and nonproductive replication pathways. The end result is that HIV-1 can sequester within the APC for several days and be transmitted via membrane extensions intracellularly and extracellularly to T cells across the virologic synapse. Virus replication requires activated T cells that can develop concurrently with the events of virus transmission. Further research is essential to fill the many gaps in our understanding of thesetransinfection processes and their role in natural HIV-1 infection.

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The critical role of human transcriptional repressor CTCF mRNA up-regulation in the induction of anti-HIV-1 responses in CD4+ T cells

Immunology Letters ◽

10.1016/j.imlet.2007.11.017 ◽

2008 ◽

Vol 117 (1) ◽

pp. 35-44 ◽

Cited By ~ 6

Author(s):

Yuchang Li ◽

Guanhua Li ◽

Anna Ivanova ◽

Sagiv Aaron ◽

Malgorzata Simm

Keyword(s):

T Cells ◽

Cd4 T Cells ◽

Critical Role ◽

Transcriptional Repressor ◽

Anti Hiv ◽

Hiv 1

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Interleukin (IL)-6 Directs the Differentiation of IL-4–producing CD4+ T Cells

Journal of Experimental Medicine ◽

10.1084/jem.185.3.461 ◽

1997 ◽

Vol 185 (3) ◽

pp. 461-470 ◽

Cited By ~ 552

Author(s):

Mercedes Rincón ◽

Juan Anguita ◽

Tetsuo Nakamura ◽

Erol Fikrig ◽

Richard A. Flavell

Keyword(s):

T Cells ◽

Cd4 T Cells ◽

Antigen Presenting Cells ◽

Interferon Γ ◽

T Helper Cell ◽

Th2 Cells ◽

T Helper ◽

Key Factor ◽

Antigen Presenting ◽

Potent Factor

Interleukin (IL)-4 is the most potent factor that causes naive CD4+ T cells to differentiate to the T helper cell (Th) 2 phenotype, while IL-12 and interferon γ trigger the differentiation of Th1 cells. However, the source of the initial polarizing IL-4 remains unclear. Here, we show that IL-6, probably secreted by antigen-presenting cells, is able to polarize naive CD4+ T cells to effector Th2 cells by inducing the initial production of IL-4 in CD4+ T cells. These results show that the nature of the cytokine (IL-12 or IL-6), which is produced by antigen-presenting cells in response to a particular pathogen, is a key factor in determining the nature of the immune response.

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CD4+ T-cell killing of multiple myeloma cells is mediated by resident bone marrow macrophages

Blood Advances ◽

10.1182/bloodadvances.2020001434 ◽

2020 ◽

Vol 4 (12) ◽

pp. 2595-2605 ◽

Cited By ~ 1

Author(s):

Ole Audun W. Haabeth ◽

Kjartan Hennig ◽

Marte Fauskanger ◽

Geir Åge Løset ◽

Bjarne Bogen ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

T Cells ◽

T Cell ◽

Cd4 T Cells ◽

Antigen Presenting Cells ◽

Bone Marrow Microenvironment ◽

Cd4 T Cell ◽

Myeloma Cells ◽

Antigen Presenting

Abstract CD4+ T cells may induce potent antitumor immune responses through interaction with antigen-presenting cells within the tumor microenvironment. Using a murine model of multiple myeloma, we demonstrated that adoptive transfer of idiotype-specific CD4+ T cells may elicit curative responses against established multifocal myeloma in bone marrow. This finding indicates that the myeloma bone marrow niche contains antigen-presenting cells that may be rendered tumoricidal. Given the complexity of the bone marrow microenvironment, the mechanistic basis of such immunotherapeutic responses is not known. Through a functional characterization of antitumor CD4+ T-cell responses within the bone marrow microenvironment, we found that killing of myeloma cells is orchestrated by a population of bone marrow–resident CD11b+F4/80+MHC-IIHigh macrophages that have taken up and present secreted myeloma protein. The present results demonstrate the potential of resident macrophages as powerful mediators of tumor killing within the bone marrow and provide a basis for novel therapeutic strategies against multiple myeloma and other malignancies that affect the bone marrow.

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DC-SIGN–mediated Infectious Synapse Formation Enhances X4 HIV-1 Transmission from Dendritic Cells to T Cells

Journal of Experimental Medicine ◽

10.1084/jem.20041356 ◽

2004 ◽

Vol 200 (10) ◽

pp. 1279-1288 ◽

Cited By ~ 182

Author(s):

Jean-François Arrighi ◽

Marjorie Pion ◽

Eduardo Garcia ◽

Jean-Michel Escola ◽

Yvette van Kooyk ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

T Cell ◽

Hiv Infection ◽

Cd4 T Cells ◽

Synapse Formation ◽

Model Systems ◽

Hiv 1 ◽

Infectious Synapse

Dendritic cells (DCs) are essential for the early events of human immunodeficiency virus (HIV) infection. Model systems of HIV sexual transmission have shown that DCs expressing the DC-specific C-type lectin DC-SIGN capture and internalize HIV at mucosal surfaces and efficiently transfer HIV to CD4+ T cells in lymph nodes, where viral replication occurs. Upon DC–T cell clustering, internalized HIV accumulates on the DC side at the contact zone (infectious synapse), between DCs and T cells, whereas HIV receptors and coreceptors are enriched on the T cell side. Viral concentration at the infectious synapse may explain, at least in part, why DC transmission of HIV to T cells is so efficient. Here, we have investigated the role of DC-SIGN on primary DCs in X4 HIV-1 capture and transmission using small interfering RNA–expressing lentiviral vectors to specifically knockdown DC-SIGN. We demonstrate that DC-SIGN− DCs internalize X4 HIV-1 as well as DC-SIGN+ DCs, although binding of virions is reduced. Strikingly, DC-SIGN knockdown in DCs selectively impairs infectious synapse formation between DCs and resting CD4+ T cells, but does not prevent the formation of DC–T cells conjugates. Our results demonstrate that DC-SIGN is required downstream from viral capture for the formation of the infectious synapse between DCs and T cells. These findings provide a novel explanation for the role of DC-SIGN in the transfer and enhancement of HIV infection from DCs to T cells, a crucial step for HIV transmission and pathogenesis.

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