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

doi:10.1007/s10875-005-4841-4

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 journal › Article › peer-review

29 Scopus citations

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 language	English (US)
Pages (from-to)	353-364
Number of pages	12
Journal	Journal of Clinical Immunology
Volume	25
Issue number	4
DOIs	https://doi.org/10.1007/s10875-005-4841-4
State	Published - Jul 2005
Externally published	Yes

Keywords

Apoptosis
Bcl-2
TGF-β
TNF-α
Tuberculosis

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1007/s10875-005-4841-4

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title = "Mechanisms of apoptosis of T-cells in human tuberculosis",

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.",

keywords = "Apoptosis, Bcl-2, TGF-β, TNF-α, Tuberculosis",

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

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T1 - Mechanisms of apoptosis of T-cells in human tuberculosis

AU - Hirsch, Christina S.

AU - Johnson, John L.

AU - Okwera, Alphonse

AU - Kanost, Richard A.

AU - Wu, Mianda

AU - Peters, Pierre

AU - Muhumuza, Mathew

AU - Mayanja-Kizza, Harriet

AU - Mugerwa, Roy D.

AU - Mugyenyi, Peter

AU - Ellner, Jerrold J.

AU - Toossi, Zahra

PY - 2005/7

Y1 - 2005/7

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Bcl-2

KW - TGF-β

KW - TNF-α

KW - Tuberculosis

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Mechanisms of apoptosis of T-cells in human tuberculosis

Abstract

Keywords

ASJC Scopus subject areas

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