Expression of costimulatory molecule CD28 on T cells in human immunodeficiency virus type 1 infection: functional and

J E Brinchmann1, J H Dobloug, B H Heger

  • 1Institute of Transplantation Immunology, National Hospital, Oslo, Norway.

Insights

Human immunodeficiency virus type 1 (HIV-1) infection impairs CD8+ T cell function, particularly those expressing CD28. Reduced CD28+ CD8+ cells correlate with HIV-related disease severity, suggesting a role in AIDS pathogenesis.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • T cell dysfunction is a hallmark of human immunodeficiency virus type 1 (HIV-1) infection.
  • The role of specific T cell subsets and costimulatory molecules in HIV-1 pathogenesis requires further elucidation.

Purpose of the Study:

  • To investigate the functional integrity of CD4+ and CD8+ T cells in individuals with HIV-1 infection.
  • To determine the impact of the costimulatory molecule CD28 on T cell function and its association with disease progression in HIV-1.

Main Methods:

  • Assessed T cell proliferation and interleukin-2 (IL-2) secretion in response to superantigens and anti-CD3/TCR antibodies.
  • Quantified CD4+ and CD8+ T cells, with a focus on CD28 expression, in HIV-1-infected individuals and controls.
  • Correlated CD28+ CD8+ cell counts with HIV-related disease status.

Main Results:

  • HIV-1 infection was associated with a functional defect in CD8+ T cells, not CD4+ T cells.
  • CD8+ T cell proliferation and IL-2 secretion were dependent on CD28 expression.
  • CD28+ CD8+ T cells were proportionally reduced in HIV-1-infected individuals.
  • In advanced immunodeficiency, even CD28+ CD8+ cells showed functional impairment.
  • A significant correlation was found between lower CD28+ CD8+ cell numbers and the presence of HIV-related disease.

Conclusions:

  • CD28 expression is critical for CD8+ T cell function in the context of HIV-1 infection.
  • The reduction and potential functional derangement of CD28+ CD8+ T cells are linked to HIV-1 pathogenesis and disease progression.
  • Regulation of CD28 expression may be a key factor in the development of Acquired Immunodeficiency Syndrome (AIDS).