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Mechanisms of Apoptosis of T-Cells in Human Tuberculosis

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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.

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Authors and Affiliations

  1. Case Western Reserve University, University Hospitals of Cleveland, Cleveland, Ohio

    Christina S. Hirsch, John L. Johnson, Richard A. Kanost, Mianda Wu & Pierre Peters

  2. Ugandan Ministry of Health, National Tuberculosis and Leprosy Programme, Kampala, Uganda

    Alphonse Okwera

  3. Joint Clinical Research Centre, Kampala, Uganda

    Mathew Muhumuza & Peter Mugyenyi

  4. Makerere University, Kampala, Uganda

    Harriet Mayanja-Kizza & Roy D. Mugerwa

  5. University of Medicine and Dentistry, Newark, New Jersey

    Jerrold J. Ellner

  6. Veterans Affairs Medical Center, Cleveland, Ohio

    Zahra Toossi

  7. Department of Medicine, Division of Infectious Diseases, BRB 10W, 10900 Euclid Ave, Cleveland, Ohio, 44106-4984

    Christina S. Hirsch

Authors
  1. Christina S. Hirsch
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  2. John L. Johnson
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  3. Alphonse Okwera
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  4. Richard A. Kanost
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  5. Mianda Wu
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  6. Pierre Peters
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  7. Mathew Muhumuza
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  8. Harriet Mayanja-Kizza
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  9. Roy D. Mugerwa
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  10. Peter Mugyenyi
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  11. Jerrold J. Ellner
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  12. Zahra Toossi
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Correspondence to Christina S. Hirsch.

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Hirsch, C.S., Johnson, J.L., Okwera, A. et al. Mechanisms of Apoptosis of T-Cells in Human Tuberculosis. J Clin Immunol 25, 353–364 (2005). https://doi.org/10.1007/s10875-005-4841-4

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  • DOI: https://doi.org/10.1007/s10875-005-4841-4

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