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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)353-364
Number of pages12
JournalJournal of Clinical Immunology
Volume25
Issue number4
DOIs
StatePublished - Jul 2005
Externally publishedYes

Keywords

  • Apoptosis
  • Bcl-2
  • TGF-β
  • TNF-α
  • Tuberculosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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