Spontaneous Secretion of Immunoglobulins and Anti-HIV-1 Antibodies by in Vivo Activated B Lymphocytes from HIV-1-Infected Subjects: Monocyte and Natural Killer Cell Requirement for in Vitro Terminal Differentiation into Plasma Cells

Fournier, Anne Marie; Fondere, Jean-Michel; Alix‐Panabières, Catherine; Merle, Corinne; Baillat, Vincent; Huguet, Marie-France; Taïb, J; Ohayon, Viviane; Zembala, Marek; Reynes, Jacques; Vendrell, Jean-François

doi:10.1006/clim.2001.5195

Cited by 25 publications

(22 citation statements)

References 56 publications

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“…Some reports suggest that DC (27,28,30,31,85,86) and B cell (35)(36)(37)(38)(39)(40)(41)(42)44) functions are altered during HIV infection. This emphasizes the need to identify ways to boost DC and B cell activities that will work in both naive and infected settings to maximally enhance the efficacy of prophylactic and therapeutic vaccines and more effectively limit HIV spread.…”

Section: Discussionmentioning

confidence: 99%

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Local and Systemic Effects of Intranodally Injected CpG-C Immunostimulatory-Oligodeoxyribonucleotides in Macaques

Teleshova

Kenney

Nest

et al. 2006

The Journal of Immunology

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Immunostimulatory CpG-C oligodeoxyribonucleotides (ISS-ODNs) represent a promising strategy to enhance vaccine efficacy. We have shown that the CpG-C ISS-ODN C274 stimulates macaque blood dendritic cells (DCs) and B cells and augments SIV-specific IFN-γ responses in vitro. To further explore the potential of C274 for future vaccine studies, we assessed the in vivo effects of locally administered C274 (in naive and healthy infected macaques). Costimulatory molecules were marginally increased on DCs and B cells within cells isolated from C274-injected lymph nodes (LNs). However, cells from C274-injected LNs exhibited heightened responsiveness to in vitro culture. This was particularly apparent at the level of CD80 (less so CD86) expression by CD123+ plasmacytoid DCs and was further boosted in the presence of additional C274 in vitro. Notably, cells from C274-injected LNs secreted significantly elevated levels of several cytokines and chemokines upon in vitro culture. This was more pronounced when cells were exposed to additional stimuli in vitro, producing IFN-α, IL-3, IL-6, IL-12, TNF-α, CCL2, CCL3, CCL5, and CXCL8. Following C274 administration in the absence of additional SIV Ag, endogenous IFN-γ secretion was elevated in LN cells of infected animals, but SIV-specific responses were unchanged. Endogenous and SIV-specific responses decreased in blood, before the SIV-specific responses rebounded by 2 wk after C274 treatment. Elevated IFN-α, CCL2, and CCL5 were also detected in the plasma after C274 injection. Thus, locally administered C274 has local and systemic activities, supporting the potential for CpG-C ISS-ODNs to boost immune function to enhance anti-HIV vaccine immunogenicity.

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Section: Discussionmentioning

confidence: 99%

“…Macaque studies also demonstrated that DC maturation and frequency in LNs are affected during SIV infection (33,34). Adding to this, several reports have indicated that B cell function is impaired in HIV-infected individuals (35)(36)(37)(38)(39)(40)(41)(42)(43)(44).…”

Section: Endritic Cells (Dcs)mentioning

confidence: 96%

Local and Systemic Effects of Intranodally Injected CpG-C Immunostimulatory-Oligodeoxyribonucleotides in Macaques

Teleshova

Kenney

Nest

et al. 2006

The Journal of Immunology

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“…In this regard, CD28 has been shown to be critical in events that lead to migration of T cells to B cell areas (40). Finally, costimulatory pathways may offer potential therapeutic avenues, especially considering numerous other studies that have shown similar APC deficiencies with monocytes and dendritic cells of HIV-infected patients (23)(24)(25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

“…Dysregulation of CD80 and CD86 expression on Ag-presenting monocytes and dendritic cells has been described in HIV infection, with predicted deleterious consequences on Ag-responsive immune competent cells including T cell apoptosis (23), induction of premature B cell terminal differentiation (24), and loss of T cell responsiveness to antigenic stimulation (25)(26)(27). Furthermore, abnormal expression of CD80 and CD86 on T cells of HIV-infected patients has been described and thought to be associated with the Department of Health and Human Services, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 effects of HIV-induced immune activation (28), similar to what occurs in other inflammatory diseases (29,30).…”

Section: H Uman Immunodeficiency Virus Infection Leads To Profound Immentioning

confidence: 99%

Deleterious Effect of HIV-1 Plasma Viremia on B Cell Costimulatory Function

Malaspina

Moir

Kottilil

et al. 2003

The Journal of Immunology

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HIV infection leads to numerous immunologic defects, including impaired B cell function. An effective humoral response requires bidirectional interactions between B cells and CD4+ T cells, critical of which are interactions between CD80/CD86 expressed on activated B cells and CD28 expressed on responder CD4+ T cells. In the present study, we examined the effect of active HIV replication on B cell costimulatory function. Induction of CD80/CD86 on B cells following B cell receptor and CD40 triggering and responsiveness of CD4+ T cells to activated B cells were investigated in a system where B cells of HIV-infected patients were compared concurrently to B cells of HIV-negative donors. In contrast to HIV-aviremic patients, B cells of HIV-viremic patients were ineffective at stimulating CD4+ T cells, as measured by the induction of activation markers and proliferation. The importance of interactions of CD80/CD86 and CD28 in activating CD4+ T cells was clear; the ablation of a normal response following the addition of neutralizing anti-CD86/CD80 Abs mirrored the response of CD4+ T cells to B cells of HIV-viremic patients, while the addition of exogenous CD28 ligands partially restored the poor CD4+ T cell response to the B cells of HIV-viremic patients. Ineffective B cell costimulatory function in HIV-viremic patients was associated with low induction of CD80/CD86 expression on B cells. Our findings further delineate the scope of defects associated with cognate B cell-CD4+ T cell interactions in HIV infection and suggest that therapeutic interventions designed to enhance CD28-dependent costimulatory pathways may help restore immune functions.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Milito

Nilsson

Titanji

et al. 2004

Blood

282

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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Spontaneous Secretion of Immunoglobulins and Anti-HIV-1 Antibodies by in Vivo Activated B Lymphocytes from HIV-1-Infected Subjects: Monocyte and Natural Killer Cell Requirement for in Vitro Terminal Differentiation into Plasma Cells

Cited by 25 publications

References 56 publications

Local and Systemic Effects of Intranodally Injected CpG-C Immunostimulatory-Oligodeoxyribonucleotides in Macaques

Local and Systemic Effects of Intranodally Injected CpG-C Immunostimulatory-Oligodeoxyribonucleotides in Macaques

Deleterious Effect of HIV-1 Plasma Viremia on B Cell Costimulatory Function

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

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