Mechanisms of apoptosis of T-cells in human tuberculosis

J Clin Immunol. 2005 Jul;25(4):353-64. doi: 10.1007/s10875-005-4841-4.


The role of TGF-beta TNF-alpha 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-beta or TNF-alpha decreased spontaneous (P < or = 0.05) and MTB-induced (P < or = 0.02) T-cell apoptosis by 50-90%, but effects were not additive. Interestingly, only levels of TGF-beta 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 < or = 0.02), and MTB stimulation reduced intracellular Bcl-2 content in CD4 T-cells from patients only (P < or = 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-beta TNF-alpha and FasL.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Apoptosis / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology*
  • Down-Regulation / immunology
  • Fas Ligand Protein / biosynthesis
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Receptors, Tumor Necrosis Factor, Type II / antagonists & inhibitors
  • Receptors, Tumor Necrosis Factor, Type II / biosynthesis
  • Transforming Growth Factor beta / biosynthesis
  • Tuberculosis, Pulmonary / immunology*
  • Tuberculosis, Pulmonary / metabolism
  • Tuberculosis, Pulmonary / pathology*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Up-Regulation / immunology
  • fas Receptor / biosynthesis
  • fas Receptor / metabolism


  • Fas Ligand Protein
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Tumor Necrosis Factor, Type II
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • fas Receptor