Mechanisms of Apoptosis of T-Cells in Human Tuberculosis
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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 WordsTuberculosis apoptosis TGF-β TNF-α Bcl-2
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- 2.Hirsch CS, Toossi Z, Othieno C, Johnson JL, Schwander SK, Robertson S, Wallis RS, Edmonds K, Okwera A, Mugerwa R, Peters P, Ellner JJ: Depressed T-cell interferon-gamma responses in pulmonary tuberculosis: Analysis of underlying mechanisms and modulation with therapy. J Infect Dis 180:2069–2073, 1999CrossRefPubMedGoogle Scholar
- 4.Hirsch CS, Toossi Z, Johnson JL, Luzze H, Ntambi L, Peters P, McHugh M, Okwera A, Joloba M, Mugyenyi P, Mugerwa RD, Terebuh P, Ellner JJ: Augmentation of apoptosis and interferon-gamma production at sites of active mycobacterium tuberculosis infection in human tuberculosis. J Infect Dis 183:779–788, 2001CrossRefPubMedGoogle Scholar
- 7.Martins GA, Vieira LQ, Cunha FQ, Silva JS: Gamma interferon modulates CD95 (Fas) and CD95 ligand (Fas-L) expression and nitric oxide-induced apoptosis during the acute phase of Trypanosoma cruzi infection: A possible role in immune response control. Infect Immun 67:3864–3871, 1999PubMedGoogle Scholar
- 16.Li B, Bassiri H, Rossman MD, Kramer P, Eyuboglu AF, Torres M, Sada E, Imir T, Carding SR: Involvement of the Fas/Fas ligand pathway in activation-induced cell death of mycobacteria-reactive human gamma delta T cells: A mechanism for the loss of gamma delta T cells in patients with pulmonary tuberculosis. J Immunol 161:1558–1567, 1998PubMedGoogle Scholar