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Journal ArticleDOI

Membrane tumour necrosis factor-α is involved in the polyclonal B-cell activation induced by HIV-infected human T cells

TLDR
It is shown that HIV-infected T-cell clones do not express the CD40 ligand (CD40L), a molecule critical for non-cognate B-cell activation, but a small proportion of them do express membrane tumour-necrosis factor (TNF)-α, which seems to be involved in the polyclonal B- cell activation induced by HIV- infected T cells.
Abstract
Infection of CD4+ T cells by human immune deficiency virus-1 (HIV-1) causes severe dysfunction of cellular immunity, but paradoxically results in intense polyclonal activation of B cells, possibly accounting for both hypergammaglobulinaemia and frequent development of B-cell malignancies seen in HIV-infected patients. We have reported that human CD4+ T-cell clones infected with HIV in vitro markedly stimulate immunoglobulin synthesis by B cells through a non-cognate, contact-dependent mechanism. We show here that HIV-infected T-cell clones do not express the CD40 ligand (CD40L), a molecule critical for non-cognate B-cell activation, but a small proportion of them do express membrane tumour-necrosis factor (TNF)-alpha. The ability of HIV-infected T-cell clones to induce polyclonal B-cell activation appears to be restricted to TNF-alpha-positive T blasts and is inhibited by antibodies against both TNF-alpha and TNF-alpha receptor. Freshly isolated CD4+ T cells from HIV-infected individuals express TNF-alpha on the cell membrane and induce TNF-alpha-mediated immunoglobulin production by B cells. Thus, membrane TNF-alpha seems to be involved in the polyclonal B-cell activation induced by HIV-infected T cells.

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Journal ArticleDOI

Activation of human dendritic cells through CD40 cross-linking.

TL;DR: It is demonstrated that dendritic Langerhans cells (D-Lc) generated by culturing cord blood CD34+ progenitor cells with granulocyte/macrophage colony-stimulating and tumor necrosis factor alpha (TNF-alpha) express functional CD40 at a density higher than that found on B cells.
Journal ArticleDOI

The CD40 Antigen and its Ligand

TL;DR: As other members of the tumor necrosis factor receptor family have been shown to bind several ligands, it is possible that CD40 may bind other ligands that may trigger CD40 on different cell types such as hematopoietic cells or epithelial cells.
Journal ArticleDOI

Immune and inflammatory responses in TNF alpha-deficient mice: a critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response.

TL;DR: A physiological role for TNF alpha in regulating the development and organization of splenic follicular architecture and in the maturation of the humoral immune response is established.
Journal ArticleDOI

Transmembrane TNF-α: structure, function and interaction with anti-TNF agents

TL;DR: The biology of transmembrane TNF-α and its interaction with anti-TNF agents will contribute to understanding the bases of differential clinical efficacy of these promising treatment modalities.
References
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Journal ArticleDOI

Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome.

TL;DR: The scope of immune dysfunction in the acquired immunodeficiency syndrome involves B cells as well as T cells, and it is concluded that the manifestations of B-cell hyperreactivity, such as hypergammaglobulinemia, seen in these patients are due to an in vivo polyclonal activation of B cells.
Journal ArticleDOI

Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS

TL;DR: An extraordinarily large number of latently infected CD4+ lymphocytes and macrophages are discovered throughout the lymphoid system from early to late stages of infection, and the extracellular association of HIV with follicular dendritic cells is confirmed.
Journal ArticleDOI

Molecular and biological characterization of a murine ligand for CD40

TL;DR: The cloning of a ligand for CD40 that is expressed on the cell surface of activated T cells and mediates B-cell proliferation in the absence of co-stimulus, as well as IgE production in the presence of interIeukin-4 is reported.
Journal ArticleDOI

Qualitative analysis of immune function in patients with the acquired immunodeficiency syndrome. Evidence for a selective defect in soluble antigen recognition.

TL;DR: The lymphocytes of patients with AIDS, although capable of undergoing a normal degree of blast transformation and lymphokine production after mitogenic stimulation, have an intrinsic defect in their ability to recognize and respond to soluble antigen.
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