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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Mechanisms of apoptosis of T-cells in human tuberculosis
Journal of Clinical Immunology, Volume 25, No. 4, Year 2005
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Description
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. © 2005 Springer Science+Business Media, Inc.
Authors & Co-Authors
Hirsch, Christina S.
United States, Cleveland
University Hospitals Case Medical Center
United States, Cleveland
Division of Infectious Diseases
Johnson, John L.
United States, Cleveland
University Hospitals Case Medical Center
Okwera, Alphonse
Uganda, Kampala
Uganda Ministry of Health
Kanost, Richard A.
United States, Cleveland
University Hospitals Case Medical Center
Wu, Mianda
United States, Cleveland
University Hospitals Case Medical Center
Peters, Pierre A.S.
United States, Cleveland
University Hospitals Case Medical Center
Muhumuza, Mathew
Uganda, Kampala
Joint Clinical Research Center Uganda
Mayanja-Kizza, Harriet
Uganda, Kampala
Makerere University
Mugerwa, Roy D.
Uganda, Kampala
Makerere University
Mugyenyi, Peter N.
Uganda, Kampala
Joint Clinical Research Center Uganda
Ellner, Jerrold J.
United States, Newark
University of Medicine and Dentistry
Toossi, Zahra T.
United States, Cleveland
Louis Stokes Cleveland va Medical Center
Statistics
Citations: 39
Authors: 12
Affiliations: 7
Identifiers
Doi:
10.1007/s10875-005-4841-4
ISSN:
02719142
Research Areas
Cancer
Infectious Diseases