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 journalArticle

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

Fingerprint

Tuberculosis
Apoptosis
T-Lymphocytes
Coculture Techniques
Neutralizing Antibodies
Messenger RNA
Proteins

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Hirsch, C. S., Johnson, J. L., Okwera, A., Kanost, R. A., Wu, M., Peters, P., ... Toossi, Z. (2005). Mechanisms of apoptosis of T-cells in human tuberculosis. Journal of Clinical Immunology, 25(4), 353-364. https://doi.org/10.1007/s10875-005-4841-4

Mechanisms of apoptosis of T-cells in human tuberculosis. / Hirsch, Christina S.; Johnson, John L.; Okwera, Alphonse; Kanost, Richard A.; Wu, Mianda; Peters, Pierre; Muhumuza, Mathew; Mayanja-Kizza, Harriet; Mugerwa, Roy D.; Mugyenyi, Peter; Ellner, Jerrold J.; Toossi, Zahra.

In: Journal of Clinical Immunology, Vol. 25, No. 4, 07.2005, p. 353-364.

Research output: Contribution to journalArticle

Hirsch, CS, Johnson, JL, Okwera, A, Kanost, RA, Wu, M, Peters, P, Muhumuza, M, Mayanja-Kizza, H, Mugerwa, RD, Mugyenyi, P, Ellner, JJ & Toossi, Z 2005, 'Mechanisms of apoptosis of T-cells in human tuberculosis', Journal of Clinical Immunology, vol. 25, no. 4, pp. 353-364. https://doi.org/10.1007/s10875-005-4841-4
Hirsch CS, Johnson JL, Okwera A, Kanost RA, Wu M, Peters P et al. Mechanisms of apoptosis of T-cells in human tuberculosis. Journal of Clinical Immunology. 2005 Jul;25(4):353-364. https://doi.org/10.1007/s10875-005-4841-4
Hirsch, Christina S. ; Johnson, John L. ; Okwera, Alphonse ; Kanost, Richard A. ; Wu, Mianda ; Peters, Pierre ; Muhumuza, Mathew ; Mayanja-Kizza, Harriet ; Mugerwa, Roy D. ; Mugyenyi, Peter ; Ellner, Jerrold J. ; Toossi, Zahra. / Mechanisms of apoptosis of T-cells in human tuberculosis. In: Journal of Clinical Immunology. 2005 ; Vol. 25, No. 4. pp. 353-364.
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