Apoptosis of macrophages and T cells in tuberculosis associated caseous necrosis

• Published in: The Journal of pathology 2000-08, Vol.191 (4), p.417-425
• Main Authors: Fayyazi, Afshin, Eichmeyer, Birgit, Soruri, Afsaneh, Schweyer, Stefan, Herms, Jochen, Schwarz, Peter, Radzun, Heinz J.
• Format: Article
• Language: English
• Subjects: apoptosis; Apoptosis - physiology; Bacterial diseases; Biological and medical sciences; caseous necrosis; CD3 Complex - metabolism; cytokine; fas Receptor - metabolism; Female; Fluorescent Antibody Technique; Human bacterial diseases; Humans; In Situ Hybridization; In Situ Nick-End Labeling; Infectious diseases; Interferon-gamma - biosynthesis; Leukocyte Common Antigens - metabolism; Macrophages - pathology; Male; Medical sciences; Microscopy, Electron; Necrosis; Proto-Oncogene Proteins c-bcl-2 - analysis; T-Lymphocytes - pathology; Tuberculoma - pathology; tuberculosis; Tuberculosis - pathology; Tuberculosis and atypical mycobacterial infections
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/1096-9896(2000)9999:9999<::AID-PATH664>3.0.CO;2-R

Immunity against mycobacteria is almost exclusively confined to epithelioid cell granulomas, where a long‐lasting but labile balance exists between host and bacilli. The relationship between immunity and mycobacteria results in regression, growth, or caseation of granulomas. To prove whether caseation is associated with apoptosis, biopsy specimens of patients with tuberculosis were analysed by electron microscopy and by in situ end‐labelling combined with immunofluorescence. Apoptotic cells were not detected in regressive granulomas. Whereas productive granulomas without histologically recognizable caseous necrosis revealed only single apoptotic cells, large numbers of apoptotic CD68+ macrophages and apoptotic CD3+, CD45RO+ T cells were observed within caseous foci. As prime candidates undergoing and/or eliciting apoptosis, vital cells surrounding caseous foci were characterized. Immunohistochemistry showed that the majority of vital CD68+ macrophages surrounding caseous foci are negative for the anti‐apoptotic protein bcl2, but positive for the pro‐apoptotic protein bax. In situ hybridization combined with immunofluorescence demonstrated that the majority of the adjacent lymphocytes are activated CD3+, CD45RO+ cells expressing the pro‐inflammatory cytokine interferon γ (IFNγ) and the death ligand FasL. These results suggest that caseation is strongly associated with apoptosis of macrophages and T lymphocytes; that the onset of apoptosis in macrophages may be promoted by the lack of bcl2 and the abundance of bax; and that activation‐induced cell death (AICD) may be responsible for the apoptosis of T cells. Copyright © 2000 John Wiley & Sons, Ltd.