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Abnormal B cell helper activity by virus-infected human CD4+ T cells

E Maggi1, F Almerigogna, G Del Prete

  • 1Immunologia Clinica e Allergologia, Istituto di Clinica Medica 3, Università di Firenze, Pisa, Italy.

Seminars in Immunology
|December 1, 1993
PubMed
Summary

Certain viral infections, like human immunodeficiency virus (HIV), can cause human CD4+ T cells to abnormally activate B cells. This abnormal B cell activation is linked to the expression of tumor necrosis factor-alpha (TNF-alpha) by infected T cells.

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Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Human immunodeficiency virus (HIV) infection disrupts normal immune function.
  • CD4+ T cells play a crucial role in orchestrating immune responses.
  • B cell activation is critical for antibody production and adaptive immunity.

Purpose of the Study:

  • To investigate the mechanism by which HIV-infected CD4+ T cells induce B cell activation.
  • To determine the role of tumor necrosis factor-alpha (TNF-alpha) in virus-induced B cell activation.
  • To explore if other viral infections induce similar abnormal T cell help.

Main Methods:

  • In vitro infection of human CD4+ T cell clones with HIV and herpesvirus saimiri (HVS).
  • Assessment of B cell proliferation and immunoglobulin production.

Related Experiment Videos

  • Analysis of TNF-alpha expression (mRNA and membrane-bound) in T cells.
  • Inhibition studies using anti-TNF-alpha antibodies.
  • Cell sorting to isolate TNF-alpha-expressing T cells.
  • Main Results:

    • HIV-infected T cells induced antigen-nonspecific B cell proliferation and immunoglobulin production without CD40 ligand expression.
    • HIV-infected T cells constitutively expressed TNF-alpha mRNA and released TNF-alpha, with some T blasts showing membrane TNF-alpha.
    • B cell activation induced by HIV-infected T cells was inhibited by anti-TNF-alpha antibodies.
    • Membrane TNF-alpha-positive T cells from HIV-infected clones retained the capacity to activate B cells.
    • HVS-infected T cells also exhibited constitutive membrane TNF-alpha and induced polyclonal B cell activation.

    Conclusions:

    • Virus-infected CD4+ T cells can provide abnormal B cell help.
    • Expression of membrane TNF-alpha by virus-infected T cells appears to mediate this abnormal B cell activation.
    • This mechanism may contribute to immune dysregulation in viral infections like HIV.