Emergence of Exhausted B Cells in Asymptomatic HIV-1-Infected Patients Naïve for HAART is Related to Reduced Immune Surveillance

Fogli, Manuela; Torti, Carlo; Malacarne, Fabio; Fiorentini, Simona; Albani, M; Izzo, Ilaria; Giagulli, Cinzia; Maggi, Fabrizio; Carosi, Giampiero; Caruso, Arnaldo

doi:10.1155/2012/829584

Cited by 34 publications

(25 citation statements)

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“…Our group and others have reported an association between TTV viraemia and the extent of immune deficiency, whether the latter is congenital (Maggi et al, 2011) or acquired (iatrogenic) Maggi et al, 2008), due to cancer (Zhong et al, 2001(Zhong et al, , 2002 or to chronic infections (Fogli et al, 2012). In 2008, we described, using a quantitative real-time PCR assay targeting conserved TTV genome regions in myeloma and lymphoma patients receiving highdose chemotherapy, a clear correlation between peaks of total TTV viraemia and expansion of senescent CD8 +…”

Section: Introductionmentioning

confidence: 59%

Short-term kinetics of torque teno virus viraemia after induction immunosuppression confirm T lymphocytes as the main replication-competent cells

Focosi¹,

Macera

Boggi

et al. 2015

Journal of General Virology

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Torque teno virus (TTV) is increasingly considered a universal marker of global immune function. The virus is supposed to replicate in lymphocytes, but poor information is available about fluctuations of viraemia after administration of anti-lymphocyte agents. We studied TTV kinetics in a cohort of 70 kidney±pancreas recipients receiving one of two different anti-T-cell induction immunosuppressants. During the first 30 days after anti-T-cell antibody administration, we report kinetics of TTV viraemia compatible with replication in T lymphocytes, and highly dependent on the potency of the anti-T-cell drug administered.

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Section: Introductionmentioning

confidence: 59%

Short-term kinetics of torque teno virus viraemia after induction immunosuppression confirm T lymphocytes as the main replication-competent cells

Focosi¹,

Macera

Boggi

et al. 2015

Journal of General Virology

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“…An exhausted B-cell phenotype has been previously associated with a CD27 − CD21 lo "tissue-like memory" B-cell subset in HIV-infected subjects [15], a subset that has been variably associated with viral load and treatment status [32,33]. This B-cell subset has been found to exhibit lesser proliferation with BCR engagement plus CD40 ligation or BCR engagement plus TLR9 ligation, but the hypoproliferative "exhausted" phenotype could be partially overcome by combining all three stimuli [15,34].…”

Section: Discussionmentioning

confidence: 99%

“…Prospective association of chronic viral antigenic stimulation (or chronic CpG or LPS exposure) leading to expansion of CD27 − CD21 − B-cells has not been established in humans. However, successful viral control under ART therapy of HIV disease has been associated with reduction of CD27 − CD21 lo B-cells in one study [32]. In HCV, CD27 − CD21 lo B-cells have been associated with virus-induced clonally expanded Bcells [17,38].…”

Section: Discussionmentioning

confidence: 99%

Peripheral CD27−CD21− B-cells represent an exhausted lymphocyte population in hepatitis C cirrhosis

Doi

Tanoue

Kaplan

2014

Clinical Immunology

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Hepatitis C cirrhosis is associated with a profound disappearance of memory B-cells. We sought to determine if this loss is associated with the expansion of the CD27 − CD21 − tissue-like memory B-cells with features of B-cell exhaustion. To this end, we quantified the frequency of CD27 − CD21 − B-cells in healthy, non-cirrhotic HCV-infected, and cirrhotic patients. We examined the expression of putative inhibitory receptors, the proliferative and immunoglobulin-secreting capacity of CD27/CD21-defined B-cell subsets upon B-cell receptor and/or CD40 stimulation. We found that CD27 − CD21 − B-cells are significantly increased in frequency relative to healthy donors in HCV-infected patients. CD27 − CD21 − B-cells were hypoproliferative relative to naïve and resting memory B-cells upon agonistic stimulation, but retained similar capacity for antibody secretion. Conclusion: CD27 − CD21 − tissue-like memory B-cells with exhausted proliferation circulate at increased frequency in cirrhotic and non-cirrhotic HCV-infected patients. This B-cell subset does not appear anergic, exhibiting immunoglobulin-secreting capacity on CD40 agonism indistinguishable from other CD27/CD21-defined B-cell subsets.

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“…CD10 staining in HIV-infected individuals can be variable. Fogli et al (18) reported previously that levels of CD21 Ϫ CD27 Ϫ tissue-like memory cells are elevated in HIVinfected patients and that these cells are essentially negative for CD10, representing an exhausted phenotype. Malaspina et al (34) reported previously that the elevated CD21 Ϫ CD27 Ϫ cell population in HIV-positive individuals could be either CD10 ϩ , representing immature cells, or CD10…”

Section: Cd20mentioning

confidence: 98%

Dynamics of Memory B-Cell Populations in Blood, Lymph Nodes, and Bone Marrow during Antiretroviral Therapy and Envelope Boosting in Simian Immunodeficiency Virus SIVmac251-Infected Rhesus Macaques

Demberg

Brocca-Cofano

Xiao

et al. 2012

J Virol

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c Human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection causes B-cell dysregulation and the loss of memory B cells in peripheral blood mononuclear cells (PBMC). These effects are not completely reversed by antiretroviral treatment (ART).To further elucidate B-cell changes during chronic SIV infection and treatment, we investigated memory B-cell subpopulations and plasma cells/plasmablasts (PC/PB) in blood, bone marrow, and lymph nodes of rhesus macaques during ART and upon release from ART. Macaques previously immunized with SIV recombinants and the gp120 protein were included to assess the effects of prior vaccination. ART was administered for 11 weeks, with or without gp120 boosting at week 9. Naïve and resting, activated, and tissue-like memory B cells and PC/PB were evaluated by flow cytometry. Antibody-secreting cells (ASC) and serum antibody titers were assessed. No lasting changes in B-cell memory subpopulations occurred in bone marrow and lymph nodes, but significant decreases in numbers of activated memory B cells and increases in numbers of tissue-like memory B cells persisted in PBMC. Macaque PC/PB were found to be either CD27 ؉ or CD27 ؊ and therefore were defined as CD19؉ . The numbers of these PC/PB were transiently increased in both PBMC and bone marrow following gp120 boosting of the unvaccinated and vaccinated macaque groups. Similarly, ASC numbers in PBMC and bone marrow of the two macaque groups also transiently increased following envelope boosting. Nevertheless, serum binding titers against SIVgp120 remained unchanged. Thus, even during chronic SIV infection, B cells respond to antigen, but long-term memory does not develop, perhaps due to germinal center destruction. Earlier and/or prolonged treatment to allow the generation of virus-specific long-term memory B cells should benefit ART/therapeutic vaccination regimens. Early and persistent B-cell dysfunction is a hallmark of human immunodeficiency virus (HIV) infection in humans (11,20,53) and precedes the loss of CD4 ϩ T cells, as shown in the simian immunodeficiency virus (SIV) rhesus macaque model (28). B-cell subpopulations and the expression of cluster-of-differentiation (CD) markers change during early HIV (22, 55) and SIV (28, 46, 58) infections. Patients on highly active antiretroviral therapy (HAART) who control viremia still exhibit B-cell dysregulation, e.g., activation, apoptosis, and abnormal CD marker expression, together with a skewing of B-cell populations, including the continued loss of memory populations and a lower frequency of naïve B cells (4,15,40,48). The early initiation of HAART might be crucial for the preservation of B-cell functionality (37), as HAART treatment has been shown to partially reverse some of these B-cell defects (43,57).Multiple studies have examined virus-specific immune responses in patients or nonhuman primates treated with antiretroviral treatment (ART) or undergoing therapeutic vaccination with or without ART. To mention a few, investigations with humans have included...

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Emergence of Exhausted B Cells in Asymptomatic HIV-1-Infected Patients Naïve for HAART is Related to Reduced Immune Surveillance

Cited by 34 publications

References 34 publications

Short-term kinetics of torque teno virus viraemia after induction immunosuppression confirm T lymphocytes as the main replication-competent cells

Short-term kinetics of torque teno virus viraemia after induction immunosuppression confirm T lymphocytes as the main replication-competent cells

Peripheral CD27−CD21− B-cells represent an exhausted lymphocyte population in hepatitis C cirrhosis

Dynamics of Memory B-Cell Populations in Blood, Lymph Nodes, and Bone Marrow during Antiretroviral Therapy and Envelope Boosting in Simian Immunodeficiency Virus SIVmac251-Infected Rhesus Macaques

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