Journal of Clinical Immunology

, Volume 25, Issue 4, pp 353–364 | Cite as

Mechanisms of Apoptosis of T-Cells in Human Tuberculosis

  • Christina S. Hirsch
  • John L. Johnson
  • Alphonse Okwera
  • Richard A. Kanost
  • Mianda Wu
  • Pierre Peters
  • Mathew Muhumuza
  • Harriet Mayanja-Kizza
  • Roy D. Mugerwa
  • Peter Mugyenyi
  • Jerrold J. Ellner
  • Zahra Toossi


The role of TGF-β TNF-α FasL and Bcl-2 in apoptosis of CD4 T-cells during active TB was studied. Coculture of PBMC from TB patients with neutralizing antibodies to TGF-β or TNF-α decreased spontaneous (P ≤ 0.05) and MTB-induced (P≤ 0.02) T-cell apoptosis by 50–90%, but effects were not additive. Interestingly, only levels of TGF-β in supernatants correlated with rates of spontaneous and MTB-induced apoptosis. FasL surface and mRNA expression were higher in unstimulated and MTB-stimulated PBMC from patients than controls, and neutralization of FasL abrogated apoptosis of T-cells from patients only. Intracellular Bcl-2 protein was lower among unstimulated CD4 T-cells from patients than those from controls (P ≤ 0.02), and MTB stimulation reduced intracellular Bcl-2 content in CD4 T-cells from patients only (P ≤ 0.001). These findings may indicate that, during TB, predisposition of CD4 T-cells to apoptosis may involve both low expression of Bcl-2, and excessive expression of TGF-β TNF-α and FasL.

Key Words

Tuberculosis apoptosis TGF-β TNF-α Bcl-2 


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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Christina S. Hirsch
    • 1
    • 7
  • John L. Johnson
    • 1
  • Alphonse Okwera
    • 2
  • Richard A. Kanost
    • 1
  • Mianda Wu
    • 1
  • Pierre Peters
    • 1
  • Mathew Muhumuza
    • 3
  • Harriet Mayanja-Kizza
    • 4
  • Roy D. Mugerwa
    • 4
  • Peter Mugyenyi
    • 3
  • Jerrold J. Ellner
    • 5
  • Zahra Toossi
    • 6
  1. 1.Case Western Reserve University, University Hospitals of ClevelandCleveland
  2. 2.Ugandan Ministry of Health, National Tuberculosis and Leprosy ProgrammeKampalaUganda
  3. 3.Joint Clinical Research CentreKampalaUganda
  4. 4.Makerere UniversityKampalaUganda
  5. 5.University of Medicine and DentistryNewark
  6. 6.Veterans Affairs Medical CenterCleveland
  7. 7.Department of MedicineDivision of Infectious DiseasesCleveland

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