Low frequency of plasma nerve-growth factor detection is associated with death of memory B lymphocytes in HIV-1 infection

Titanji, Kehmia; Nilsson, Anna; Mörch, C.; Samuelsson, Astrid; Sönnerborg, Anders; Grützmeier, Sven; Zazzi, Maurizio; Milito, Angelo De

doi:10.1046/j.1365-2249.2003.02145.x

Cited by 25 publications

(30 citation statements)

References 38 publications

(51 reference statements)

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“…This approach required that HIV-specific B cells not only survive the in vitro culture period but also respond to the stimulation by undergoing terminal differentiation. There is good reason to believe that memory B cells of HIV-infected viremic individuals may be defective in these ex vivo processes, given their increased propensity to undergo apoptosis compared with memory B cells from HIV-uninfected and HIV-aviremic individuals (49)(50)(51)(52). The recent development of trimeric HIV envelope probes that can measure directly HIV-specific B cells (15), without in vitro manipulation, represents a major advancement for studying humoral immunity against the virus.…”

Section: Discussionmentioning

confidence: 99%

Abnormal B cell memory subsets dominate HIV-specific responses in infected individuals

Kardava¹,

Moir²,

Shah³

et al. 2014

J. Clin. Invest.

123

186

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Section: Discussionmentioning

confidence: 99%

Abnormal B cell memory subsets dominate HIV-specific responses in infected individuals

Kardava¹,

Moir²,

Shah³

et al. 2014

J. Clin. Invest.

123

186

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“…We recently reported that memory B lymphocytes from HIV-1-infected subjects undergo spontaneous apoptosis in vitro, 6,30 suggesting that this alteration may account for the dysfunctions in humoral immunity. Many studies have indicated a defect in the humoral immunity toward several antigens 9,11,26,27 and such a defect may be due to the deletion of antigen-specific CD4 ϩ T cells or to the loss of memory B cells.…”

Section: Discussionmentioning

confidence: 99%

“…We have recently reported that the reduction of circulating memory B cells observed in HIV-1 infection is associated with a significant increase of spontaneous cell death in vitro of memory B lymphocytes. 6,30 In the populations described here we confirm that memory B lymphocytes are reduced in HIV-1 infection as compared with uninfected controls (20% [range, 6.8%-43%] vs 34.3%, [range, 21.1%-60.7%]; P Ͻ .001) and that these cells exhibit higher spontaneous apoptosis as compared with the cells from healthy subjects (26.2% Ϯ 2.5% vs 7.9% Ϯ 1.4%; P Ͻ .001). Moreover, regression analysis performed on treatment-naive patients showed that the percentage of memory B cells inversely correlates with the HIV-1 plasma viral load (r ϭ 0.45, P ϭ .02).…”

Section: Loss Of Antigen-specific Humoral Immunity In Hiv-1 Infectionmentioning

confidence: 99%

“…6,30 The loss of memory B cells may be mediated by overexpression of CD70 on activated T lymphocytes 6,31 which may induce terminal differentiation to plasma cells and/or by lack of survival factors leading to apoptosis. 30 In the present study, we investigated the phenotype and function of naive B cells isolated from HIV-1-infected persons and evaluated the status of antigen-specific humoral immunity in relation to hypergammaglobulinemia and loss of memory B cells. The results of our study indicate that hyperactivated naive B cells may significantly contribute to hypergammaglobulinemia and autoantibody production.…”

Section: Introductionmentioning

confidence: 99%

“…28,29 We have recently shown that memory B lymphocytes are significantly reduced during HIV-1 infection and are prone to undergo spontaneous apoptosis in vitro. 6,30 The loss of memory B cells may be mediated by overexpression of CD70 on activated T lymphocytes 6,31 which may induce terminal differentiation to plasma cells and/or by lack of survival factors leading to apoptosis. 30 In the present study, we investigated the phenotype and function of naive B cells isolated from HIV-1-infected persons and evaluated the status of antigen-specific humoral immunity in relation to hypergammaglobulinemia and loss of memory B cells.…”

mentioning

confidence: 99%

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Mechanisms of hypergammaglobulinemia and impaired antigen-specific humoral immunity in HIV-1 infection

Milito

Nilsson

Titanji

et al. 2004

Blood

280

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IntroductionA profound impairment of immune functions occurs in individuals infected with human immunodeficiency virus type 1 (HIV-1). Both the cellular and the humoral arms of the immune system are unable to control the infection, which ultimately results in severe exhaustion of several lymphocyte functions and increased susceptibility to secondary and opportunistic infections. Major immunologic defects occur in the B-cell compartment. 1 Polyclonal B-cell activation is demonstrated by hypergammaglobulinemia and spontaneous antibodies' (Abs) production by cultured peripheral lymphocytes 2,3 ; additional signs of B-cell abnormality are the high incidence of B-cell tumors 4 and the deregulated expression of several surface molecules like Fas, Fas ligand (FasL), CD5, CD21, and CD27. 5-8 B-cell hyperactivity is also accompanied by functional defects since humoral immune responses following immunization are severely impaired in HIV-1-infected subjects and B lymphocytes from patients are poorly responsive to in vitro stimulation. [9][10][11] Several mechanisms may account for the B-cell abnormalities in HIV-1 infection. A direct effect of virus replication or viral proteins on B-cell function has been shown 12 and sustained by the observation that polyclonal B-cell activation is strongly reduced following effective antiretroviral treatment. 13-15 HIV-driven unbalanced production of several cytokines like tumor necrosis factor ␣ (TNF-␣), interleukin 6 (IL-6), IL-10, and IL-15 has also been involved in B-cell dysfunctions. [16][17][18] Defective T-cell help may account for B-cell unresponsiveness to T-cell-dependent antigens. 19,20 The defect of B cells in HIV-1 infection appears, however, to be intrinsic since it begins early during infection preceding functional and quantitative defects in T-helper activity and cannot be restored by allogenic normal CD4 ϩ T cells in vitro. 3,21 The mechanisms inducing hypergammaglobulinemia in HIV-1 infection are only partially known. Activation driven by CD4 ϩ T cells, monocytes, and natural killer (NK) cells through CD40-CD40 ligand (CD40L) interaction and an inappropriate cytokine supply may have a relevant role in inducing abnormal differentiation of B cells. 17,22 In addition, HIV-1 itself may directly affect B-cell activation and dysfunction, inducing the appearance of a subset of CD21 Ϫ B cells which have been proposed to contribute to increased antibody production. 23,24 A recent work by Hunziker et al 25 has suggested that naive B cells represent an important source of hypergammaglobulinemia and autoantibody production in chronic viral infections.Because of the lack of protective humoral immunity, HIV-1-infected individuals receive vaccination against several pathogens. However, many studies have reported an impaired humoral immune response in most of the patients after vaccination. [9][10][11]26,27 From the Microbiology and Tumor Biology Center, Karolinska Institutet, and the Gay Men's Health Clinic, The Soder Hospital, Stockholm, Sweden; the Swedish Institute for Infectious...

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The delicate balance between neurotoxicity and neuroprotection in the context of HIV‐1 infection

Sénécal

Barat

Tremblay

2020

Glia

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Human immunodeficiency virus type-1 (HIV-1) causes a spectrum of neurological impairments, termed HIV-associated neurocognitive disorder (HAND), following the infiltration of infected cells into the brain. Even though the implementation of antiretroviral therapy reduced the systemic viral load, the prevalence of HAND remains unchanged and infected patients develop persisting neurological disturbances affecting their quality of life. As a result, HAND have gained importance in basic and clinical researches, warranting the need of developing new adjunctive treatments. Nonetheless, a better understanding of the molecular and cellular mechanisms remains necessary. Several studies consolidated their efforts into elucidating the neurotoxic signaling leading to HAND including the deleterious actions of HIV-1 viral proteins and inflammatory mediators. However, the scope of these studies is not sufficient to address all the complexity related to HAND development. Fewer studies focused on an altered neuroprotective capacity of the brain to respond to HIV-1 infection. Neurotrophic factors are endogenous polyproteins involved in neuronal survival, synaptic plasticity, and neurogenesis. Any defects in the processing or production of these crucial factors might compose a risk factor rendering the brain more vulnerable to neuronal damages. Due to their essential roles, they have been investigated for their diverse interplays with HIV-1 infection. In this review, we present a complete description of the neurotrophic factors involved in HAND. We discuss emerging concepts for their therapeutic applications and summarize the complex mechanisms that down-regulate their production in favor of a neurotoxic environment. For certain factors, we finally address opposing roles that rather lead to increased inflammation.

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Low frequency of plasma nerve-growth factor detection is associated with death of memory B lymphocytes in HIV-1 infection

Cited by 25 publications

References 38 publications

Abnormal B cell memory subsets dominate HIV-specific responses in infected individuals

Abnormal B cell memory subsets dominate HIV-specific responses in infected individuals

Mechanisms of hypergammaglobulinemia and impaired antigen-specific humoral immunity in HIV-1 infection

The delicate balance between neurotoxicity and neuroprotection in the context of HIV‐1 infection

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