Control of HIV infection: Escape from the shadow of Blimp‐1

Thaventhiran, James; Fearon, Douglas T.

doi:10.1002/eji.201243263

Cited by 10 publications

(10 citation statements)

References 29 publications

(37 reference statements)

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“…The expression of BLIMP-1 can be modulated at the translational level by microRNA-mir9 and Seddiki et al demonstrated that BLIMP-1 levels decreased following treatment with pre-mir-9, while IL-2 expression was increased. Levels of mir-9 were also found to be elevated in LTNP compared to chronically infected subjects ( 191 , 192 ). BLIMP-1 has also been found to be required for effector Treg differentiation and is essential for IL-10 production ( 193 ).…”

Section: Role Of Transcription Factorsmentioning

confidence: 89%

CD4 T Cells Mediate Both Positive and Negative Regulation of the Immune Response to HIV Infection: Complex Role of T Follicular Helper Cells and Regulatory T Cells in Pathogenesis

Phetsouphanh

Zaunders

2015

Front. Immunol.

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HIV-1 infection results in chronic activation of cells in lymphoid tissue, including T cells, B-cells, and myeloid lineage cells. The resulting characteristic hyperplasia is an amalgam of proliferating host immune cells in the adaptive response, increased concentrations of innate response mediators due to viral and bacterial products, and homeostatic responses to inflammation. While it is generally thought that CD4 T cells are greatly depleted, in fact, two types of CD4 T cells appear to be increased, namely, regulatory T cells (Tregs) and T follicular helper cells (Tfh). These cells have opposing roles, but may both be important in the pathogenic process. Whether Tregs are failing in their role to limit lymphocyte activation is unclear, but there is no doubt now that Tfh are associated with B-cell hyperplasia and increased germinal center activity. Antiretroviral therapy may reduce the lymphocyte activation, but not completely, and therefore, there is a need for interventions that selectively enhance normal CD4 function without exacerbating Tfh, B-cell, or Treg dysfunction.

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Section: Role Of Transcription Factorsmentioning

confidence: 89%

CD4 T Cells Mediate Both Positive and Negative Regulation of the Immune Response to HIV Infection: Complex Role of T Follicular Helper Cells and Regulatory T Cells in Pathogenesis

Phetsouphanh

Zaunders

2015

Front. Immunol.

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“…IL-2-induced expression of BLIMP-1 is repressed by upregulation of miR-9, which leads to reduced binding of BLIMP-1 to the IL2 promoter. Published studies have further identified that a regulatory miR-9/Blimp-1/IL-2 pathway is impaired in progressive HIV disease [21, 62]. Low expression of PRDM1 was associated with high HIV genome transcription levels in resting CD4 + CM T cells, suggesting that BLIMP-1 might be involved in controlling the HIV reservoirs in the CM T cell subset [63].…”

Section: Genetic Disruption Of Blimp-1 In T Cells and Its Effect On Pmentioning

confidence: 99%

New insights into Blimp-1 in T lymphocytes: a divergent regulator of cell destiny and effector function

Yeh

Chu

et al. 2017

J Biomed Sci

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B lymphocyte-induced maturation protein-1 (Blimp-1) serves as a master regulator of the development and function of antibody-producing B cells. Given that its function in T lymphocytes has been identified within the past decade, we review recent findings with emphasis on its role in coordinated control of gene expression during the development, differentiation, and function of T cells. Expression of Blimp-1 is mainly confined to activated T cells and is essential for the production of interleukin (IL)-10 by a subset of forkhead box (Fox)p3+ regulatory T cells with an effector phenotype. Blimp-1 is also required to induce cell elimination in the thymus and critically modulates peripheral T cell activation and proliferation. In addition, Blimp-1 promotes T helper (Th) 2 lineage commitment and limits Th1, Th17 and follicular helper T cell differentiation. Furthermore, Blimp-1 coordinates with other transcription factors to regulate expression of IL-2, IL-21 and IL-10 in effector T lymphocytes. In CD8+ T cells, Blimp-1 expression is distinct in heterogeneous populations at the stages of clonal expansion, differentiation, contraction and memory formation when they encounter antigens. Moreover, Blimp-1 plays a fundamental role in coordinating cytokine receptor signaling networks and transcriptional programs to regulate diverse aspects of the formation and function of effector and memory CD8+ T cells and their exhaustion. Blimp-1 also functions as a gatekeeper of T cell activation and suppression to prevent or dampen autoimmune disease, antiviral responses and antitumor immunity. In this review, we discuss the emerging roles of Blimp-1 in the complex regulation of gene networks that regulate the destiny and effector function of T cells and provide a Blimp-1-dominated transcriptional framework for T lymphocyte homeostasis.

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“…While lack of BLIMP-1 gives defective cytolytic function in virus-specific CD8 + T cells and low expression of KLRG1 [77], the potential role of BLIMP-1 in the upregulation of multiple inhibitory molecules is clear in chronic viral infections, especially in LCMV and HIV-1 infection [2,4,63,103]. We have demonstrated that BLIMP-1 is induced in CD4 + T cells stimulated by HIV-exposed DCs [2,4] and recent lines of evidence points to the existence of a novel miR-9/BLIMP-1/IL-2 axis that is compromised in progressive HIV disease but not in LTNPs [104,105]. BLIMP-1 is upregulated in CD4 + T cells via TCR stimulation and IL-2 and this is regulated by miR-9 levels.…”

Section: Reviewmentioning

confidence: 99%

“…BLIMP-1 is upregulated in CD4 + T cells via TCR stimulation and IL-2 and this is regulated by miR-9 levels. The upregulation of miR-9 induces BLIMP-1 repression, leading to restoration of IL-2 secretion by CD4 + T cells, which occurs by reduced binding potential of BLIMP-1 to the il-2 promoter [104,105]. …”

Section: Reviewmentioning

confidence: 99%

Molecular signatures of T-cell inhibition in HIV-1 infection

et al. 2013

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Cellular immune responses play a crucial role in the control of viral replication in HIV-infected individuals. However, the virus succeeds in exploiting the immune system to its advantage and therefore, the host ultimately fails to control the virus leading to development of terminal AIDS. The virus adopts numerous evasion mechanisms to hijack the host immune system. We and others recently described the expression of inhibitory molecules on T cells as a contributing factor for suboptimal T-cell responses in HIV infection both in vitro and in vivo. The expression of these molecules that negatively impacts the normal functions of the host immune armory and the underlying signaling pathways associated with their enhanced expression need to be discussed. Targets to restrain the expression of these molecular markers of immune inhibition is likely to contribute to development of therapeutic interventions that augment the functionality of host immune cells leading to improved immune control of HIV infection. In this review, we focus on the functions of inhibitory molecules that are expressed or secreted following HIV infection such as BTLA, CTLA-4, CD160, IDO, KLRG1, LAG-3, LILRB1, PD-1, TRAIL, TIM-3, and regulatory cytokines, and highlight their significance in immune inhibition. We also highlight the ensemble of transcriptional factors such as BATF, BLIMP-1/PRDM1, FoxP3, DTX1 and molecular pathways that facilitate the recruitment and differentiation of suppressor T cells in response to HIV infection.

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Control of HIV infection: Escape from the shadow of Blimp‐1

Cited by 10 publications

References 29 publications

CD4 T Cells Mediate Both Positive and Negative Regulation of the Immune Response to HIV Infection: Complex Role of T Follicular Helper Cells and Regulatory T Cells in Pathogenesis

CD4 T Cells Mediate Both Positive and Negative Regulation of the Immune Response to HIV Infection: Complex Role of T Follicular Helper Cells and Regulatory T Cells in Pathogenesis

New insights into Blimp-1 in T lymphocytes: a divergent regulator of cell destiny and effector function

Molecular signatures of T-cell inhibition in HIV-1 infection

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