scholarly journals Dendritic Cells Enhance HIV Infection of Memory CD4+T Cells in Human Lymphoid Tissues

2016 ◽  
Vol 32 (2) ◽  
pp. 203-210 ◽  
Author(s):  
Angel L. Reyes-Rodriguez ◽  
Morgan A. Reuter ◽  
David McDonald
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Hiv Infection ◽  
Cd4 T Cells ◽  
Lymphoid Tissues ◽  
Memory Cd4 T Cells

scholarly journals Endogenous factors enhance HIV infection of tissue naive CD4 T cells by stimulating high molecular mass APOBEC3G complex formation

2006 ◽  
Vol 203 (4) ◽  
pp. 865-870 ◽  
Author(s):  
Jason F. Kreisberg ◽  
Wes Yonemoto ◽  
Warner C. Greene
Keyword(s):  
T Cells ◽  
Hiv Infection ◽  
Molecular Mass ◽  
Cd4 T Cells ◽  
Molecular Mechanisms ◽  
High Molecular Mass ◽  
Lymphoid Tissues ◽  
Soluble Factors ◽  
Endogenous Factors ◽  
Memory Cd4 T Cells

Human immunodeficiency virus (HIV) can infect resting CD4 T cells residing in lymphoid tissues but not those circulating in peripheral blood. The molecular mechanisms producing this difference remain unknown. We explored the potential role of the tissue microenvironment and its influence on the action of the antiviral factor APOBEC3G (A3G) in regulating permissivity to HIV infection. We found that endogenous IL-2 and -15 play a key role in rendering resident naive CD4 T cells susceptible to HIV infection. Infection of memory CD4 T cells also requires endogenous soluble factors, but not IL-2 or -15. A3G is found in a high molecular mass complex in HIV infection–permissive, tissue-resident naive CD4 T cells but resides in a low molecular mass form in nonpermissive, blood-derived naive CD4 T cells. Upon treatment with endogenous soluble factors, these cells become permissive for HIV infection, as low molecular mass A3G is induced to assemble into high molecular mass complexes. These findings suggest that in lymphoid tissues, endogenous soluble factors, likely including IL-2 and -15 and others, stimulate the formation of high molecular mass A3G complexes in tissue-resident naive CD4 T cells, thereby relieving the potent postentry restriction block for HIV infection conferred by low molecular mass A3G.

scholarly journals Plasmacytoid dendritic cells have divergent effects on HIV infection of initial target cells and induce a pro-retention phenotype

2021 ◽  
Vol 17 (4) ◽  
pp. e1009522
Author(s):  
Orion Tong ◽  
Gabriel Duette ◽  
Thomas Ray O’Neil ◽  
Caroline M. Royle ◽  
Hafsa Rana ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Reverse Transcriptase ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Target Cells ◽  
Ccr5 Expression ◽  
Memory Cd4 T Cells

Although HIV infection inhibits interferon responses in its target cells in vitro, interferon signatures can be detected in vivo soon after sexual transmission, mainly attributed to plasmacytoid dendritic cells (pDCs). In this study, we examined the physiological contributions of pDCs to early HIV acquisition using coculture models of pDCs with myeloid DCs, macrophages and the resting central, transitional and effector memory CD4 T cell subsets. pDCs impacted infection in a cell-specific manner. In myeloid cells, HIV infection was decreased via antiviral effects, cell maturation and downregulation of CCR5 expression. In contrast, in resting memory CD4 T cells, pDCs induced a subset-specific increase in intracellular HIV p24 protein expression without any activation or increase in CCR5 expression, as measured by flow cytometry. This increase was due to reactivation rather than enhanced viral spread, as blocking HIV entry via CCR5 did not alter the increased intracellular p24 expression. Furthermore, the load and proportion of cells expressing HIV DNA were restricted in the presence of pDCs while reverse transcriptase and p24 ELISA assays showed no increase in particle associated reverse transcriptase or extracellular p24 production. In addition, PDCs also markedly induced the expression of CD69 on infected CD4 T cells and other markers of CD4 T cell tissue retention. These phenotypic changes showed marked parallels with resident memory CD4 T cells isolated from anogenital tissue using enzymatic digestion. Production of IFNα by pDCs was the main driving factor for all these results. Thus, pDCs may reduce HIV spread during initial mucosal acquisition by inhibiting replication in myeloid cells while reactivating latent virus in resting memory CD4 T cells and retaining them for immune clearance.

scholarly journals Correction: Understanding the Slow Depletion of Memory CD4+ T Cells in HIV Infection

PLoS Medicine ◽  
2008 ◽  
Vol 5 (1) ◽  
pp. e11 ◽  
Author(s):  
Andrew Yates ◽  
Jaroslav Stark ◽  
Nigel Klein ◽  
Rustom Antia ◽  
Robin Callard
Keyword(s):  
T Cells ◽  
Hiv Infection ◽  
Cd4 T Cells ◽  
Memory Cd4 T Cells

Transcription factor FOXO3a controls the persistence of memory CD4+ T cells during HIV infection

2008 ◽  
Vol 14 (3) ◽  
pp. 266-274 ◽  
Author(s):  
Julien van Grevenynghe ◽  
Francesco A Procopio ◽  
Zhong He ◽  
Nicolas Chomont ◽  
Catherine Riou ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
Hiv Infection ◽  
Cd4 T Cells ◽  
Memory Cd4 T Cells

scholarly journals Dexamethasone and Monophosphoryl Lipid A-Modulated Dendritic Cells Promote Antigen-Specific Tolerogenic Properties on Naive and Memory CD4+ T Cells

2016 ◽  
Vol 7 ◽  
Author(s):  
Jaxaira Maggi ◽  
Katina Schinnerling ◽  
Bárbara Pesce ◽  
Catharien M. Hilkens ◽  
Diego Catalán ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd4 T Cells ◽  
Lipid A ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Memory Cd4 T Cells

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

2004 ◽  
Vol 200 (10) ◽  
pp. 1279-1288 ◽  
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.

scholarly journals Cofilin hyperactivation in HIV infection and targeting the cofilin pathway using an anti-α4β7 integrin antibody

2019 ◽  
Vol 5 (1) ◽  
pp. eaat7911 ◽  
Author(s):  
Sijia He ◽  
Yajing Fu ◽  
Jia Guo ◽  
Mark Spear ◽  
Jiuling Yang ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Migration ◽  
T Cell ◽  
Hiv Infection ◽  
Cell Motility ◽  
Cd4 T Cells ◽  
Immune Reconstitution ◽  
Actin Dynamics ◽  
Lymphoid Tissues ◽  
Cell Recovery

A functional HIV cure requires immune reconstitution for lasting viremia control. A major immune dysfunction persisting in HIV infection is the impairment of T helper cell migration and homing to lymphoid tissues such as GALTs (gut-associated lymphoid tissues). ART (antiretroviral therapy) does not fully restore T cell motility for tissue repopulation. The molecular mechanism dictating this persistent T cell dysfunction is not understood. Cofilin is an actin-depolymerizing factor that regulates actin dynamics for T cell migration. Here, we demonstrate that blood CD4 T cells from HIV-infected patients (n = 193), with or without ART, exhibit significantly lower levels of cofilin phosphorylation (hyperactivation) than those from healthy controls (n = 100; ratio, 1.1:2.3; P < 0.001); cofilin hyperactivation is also associated with poor CD4 T cell recovery following ART. These results suggest an HIV-mediated systemic dysregulation of T cell motility that cannot be repaired solely by ART. We further demonstrate that stimulating blood CD4 T cells with an anti–human α4β7 integrin antibody can trigger signal transduction and modulate the cofilin pathway, partially restoring T cell motility in vitro. However, we also observed that severe T cell motility defect caused by high degrees of cofilin hyperactivation was not repairable by the anti-integrin antibody, demonstrating a mechanistic hindrance to restore immune functions in vivo. Our study suggests that cofilin is a key molecule that may need to be therapeutically targeted early for T cell tissue repopulation, immune reconstitution, and immune control of viremia.

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