Immune activation and increased IL‐21R expression are associated with the loss of memory B cells during HIV‐1 infection

Ruffin, Nicolas; Lantto, Rebecka; Pensieroso, Simone; Sammicheli, Stefano; Hejdeman, Bo; Réthi, Bence; Chiodi, Francesca

doi:10.1111/j.1365-2796.2012.02550.x

Cited by 14 publications

(12 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TLR stimulation, together with CD40L, induces IL-10 production by human B cells in vitro. Stimulation through TLRs on B cells during HIV-1 infection may induce Breg cells in these patients; in this context, it is still poorly understood how microbial translocation taking place through the fenestrated intestinal barrier during HIV-1 infection may contribute to increased TLR stimulation of B cells leading to alteration of B-cell phenotype and functions [41] (Fig. 3).…”

Section: Production Of Interleukin-10 Characterizes Regulatory B Cellsmentioning

confidence: 99%

“…They may result from increased susceptibility to apoptosis due to altered expression of receptors important for survival and cell death [7,[40][41][42], altered homing to and presence within the lymphoid tissue as a consequence of altered expression of molecules pivotal for homing of B cells, for example, CXCR5/CXCL13 [43] and/or increased differentiation of B cells toward plasma cells [10]. Studies on population dynamics of the B-cell compartment may contribute to new and important explanations for the changes in proportions of B-cell subpopulations during HIV-1 infection.…”

Section: Redistribution Of Classic and Rare Populations Of Memory B Cmentioning

confidence: 99%

See 1 more Smart Citation

Impairment of B-cell functions during HIV-1 infection

Amu

Ruffin

Réthi

et al. 2013

Aids

View full text Add to dashboard Cite

A variety of B-cell dysfunctions are manifested during HIV-1 infection, as reported early during the HIV-1 epidemic. It is not unusual that the pathogenic mechanisms presented to elucidate impairment of B-cell responses during HIV-1 infection focus on the impact of reduced T-cell numbers and functions, and lack of germinal center formation in lymphoid tissues. To our understanding, however, perturbation of B-cell phenotype and function during HIV-1 infection may begin at several different B-cell developmental stages. These impairments can be mediated by intrinsic B-cell defects as well as by the lack of proper T-cell help. In this review, we will highlight some of the pathways and molecular interactions leading to B-cell impairment prior to germinal center formation and B-cell activation mediated through the B-cell receptor in response to HIV-1 antigens. Recent studies indicate a regulatory role for B cells on T-cell biology and immune responses. We will discuss some of these novel findings and how these regulatory mechanisms could potentially be affected by the intrinsic defects of B cells taking place during HIV-1 infection.

show abstract

Section: Production Of Interleukin-10 Characterizes Regulatory B Cellsmentioning

confidence: 99%

Section: Redistribution Of Classic and Rare Populations Of Memory B Cmentioning

confidence: 99%

Impairment of B-cell functions during HIV-1 infection

Amu

Ruffin

Réthi

et al. 2013

Aids

View full text Add to dashboard Cite

show abstract

“…Several mechanisms account for memory B cell depletion and dysfunction in HIV disease, including less CD4 T cell help, binding to CD21 and direct activation of B cells by HIV, [69–72] polyclonal activation of B cells, [73,74] indirect induction of B cell apoptosis by IL-7, [73,75,76] impaired traffcking and differentiation of B cells, [77] and dysfunction of T follicular helper cells [78,79]. As a consequence of impaired antigen-specific B cell antibody production, the integrity of the gut mucosa is further impaired [80].…”

Section: B Cell Perturbations In Hiv Diseasementioning

confidence: 99%

Microbial TLR Agonists and Humoral Immunopathogenesis in HIV Disease

Zhou

et al. 2013

Epidemiology

View full text Add to dashboard Cite

Although T cells are the primary and most-studied targets of the Human Immunodeficiency Virus (HIV), B cells, especially memory B lymphocytes, are also chronically depleted in the course of HIV disease. Although the lack of CD4+ T cell help may explain these deficiencies, intrinsic defects in B lymphocytes appear to contribute to B cell depletion and reduced antibody (Ab) production in the setting of HIV, especially of some antigens eliciting T cell-independent responses. The gut mucosal barrier is disrupted in HIV disease, resulting in increased systemic exposure to microbial products such as Toll-Like Receptor (TLR) agonists. The association of enhanced systemic levels of TLR agonists and B cell dysfunction in HIV disease is not understood. This review discusses the potential role of microbial TLR agonists in the B cell depletion, enhanced autoantibody production and impaired responses to vaccination observed in HIV-infected hosts. Increased microbial translocation in HIV infection may drive B cells to produce autoantibodies and increase susceptibilities of B cells to apoptosis through activation-induced cell death. Determining the mechanisms of B cell perturbations in HIV disease will inform the design of novel strategies of improve immune responses to vaccines, reduce opportunistic infections and slow disease progression.

show abstract

“…It effectively enhances T cell proliferation and the killing function of NK cells, resulting in a strong antitumor immune response (4,5). Its receptor (IL-21R) is widely expressed in various cell types within the immune system, including NK cells, B cells, T cells, macrophages and dendritic cells (6–8). The widespread lymphoid distribution of the IL-21R leads to pleiotropic action of IL-21 in the innate and adaptive immune responses (6–8).…”

Section: Introductionmentioning

confidence: 99%

“…Its receptor (IL-21R) is widely expressed in various cell types within the immune system, including NK cells, B cells, T cells, macrophages and dendritic cells (6–8). The widespread lymphoid distribution of the IL-21R leads to pleiotropic action of IL-21 in the innate and adaptive immune responses (6–8). For this reason, researchers are becoming increasingly interested in IL-21.…”

Section: Introductionmentioning

confidence: 99%

Adenovirus-mediated interleukin 21 gene transfer enhances antitumor immunity and reduces tumorigenicity of Hepa1–6 in mice

Wang

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

In the present study, adenovirus-mediated interleukin 21 (Ad5-IL-21-EGFP) gene expression was induced in Hepa1–6 cells to investigate whether IL-21 was capable of enhancing antitumor immunity and reducing tumorigenicity of Hepa1–6 in a mouse model. Mice were inoculated intradermally into the right flank with Hepa1–6 cells or Hepa1–6 cells infected with Ad5 or Ad5-IL-21. Four weeks later, the mice were sacrificed humanely, and the tumor volume, tumor weight and mouse spleen index were measured. The levels of IL-21, IL-4 and interferon (IFN)-γ levels in mouse serum and tumor tissues were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. Cell counting kit-8 (CCK-8) assay was used to detect the killing ability of spleen T cells and natural killer (NK) cells, and the proliferation ability of T cells. The expression of IL-21 was confirmed by reverse transcription-polymerase chain reaction, western blot analysis and ELISA assay in Ad5-IL-21-EGFP-infected Hepa1–6 cells. The overexpression of IL-21 significantly reduced the tumorigenicity of Hepa1–6 cells. The tumor volumes and tumor weights in Ad5-IL-21-Hepa1–6 mice were much smaller than those in the Ad5-Hepa1–6 group and Hepa1–6 wild-type group. The immunohistochemistry and ELISA assay demonstrated that IL-21 and IFN-γ levels were much higher while the IL-4 level was much lower in the Ad5-IL-21-Hepa1–6 group than in the other two groups. CCK-8 assay revealed that the killing ability of NK cells and T cells, and the proliferation ability of T cells in Ad5-IL-21-Hepa1–6 mice were higher than in the other two groups; the spleen index of Ad5-IL-21-Hepa1–6 mice was also higher than in the other groups. The data had a significant difference (P<0.01). In conclusion, IL-21 reduces tumorigenicity of Hepa1–6 by a mechanism involving enhanced activation of cell-mediated immunity in tumor-bearing mice.

show abstract

Immune activation and increased IL‐21R expression are associated with the loss of memory B cells during HIV‐1 infection

Cited by 14 publications

References 49 publications

Impairment of B-cell functions during HIV-1 infection

Impairment of B-cell functions during HIV-1 infection

Microbial TLR Agonists and Humoral Immunopathogenesis in HIV Disease

Adenovirus-mediated interleukin 21 gene transfer enhances antitumor immunity and reduces tumorigenicity of Hepa1–6 in mice

Contact Info

Product

Resources

About