Cell proliferation and apoptosis: dual-signal hypothesis tested in tuberculous pleuritis using mycobacterial antigens

• Published in: FEMS immunology and medical microbiology 2004-05, Vol.41 (1), p.85-92
• Main Authors: Das, Sulochana D., Subramanian, Deepa, Prabha, C.
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal; Antigens; Antigens, Bacterial - immunology; Apoptosis; Bacterial diseases; Biological and medical sciences; CD3 antigen; CD3 Complex - analysis; Cell activation; Cell cycle; Cell Division; Cell growth; Cell proliferation; Correlation analysis; Dexamethasone; DNA Fragmentation; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Human bacterial diseases; Humans; Hypotheses; Immune response; In vivo methods and tests; Infectious diseases; Interphase; Kinetics; Leukocytes (mononuclear); Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - physiology; Lymphocyte Activation; Lymphocyte transformation; Lymphocytes; Medical sciences; Microbiology; Mitogens; Mycobacterial antigens; Mycobacterium tuberculosis; Mycobacterium tuberculosis - immunology; Peripheral blood mononuclear cells; Phytohemagglutinins - immunology; Pleural fluid; Pleurisy; Tuberculin - immunology; Tuberculosis; Tuberculosis and atypical mycobacterial infections; Tuberculosis, Pleural - blood; Tuberculosis, Pleural - immunology; Tuberculosis, Pleural - physiopathology; Tuberculous pleuritis
• ISSN: 0928-8244; 1574-695X; 2049-632X
• DOI: 10.1016/j.femsim.2004.01.006

Antigens and mitogens have the innate ability to trigger cell proliferation and apoptosis thus exhibiting a dual-signal phenomenon. This dual-signal hypothesis was tested with mycobacterial antigens (PPD and heat killed Mycobacterium tuberculosis – MTB) in tuberculous pleuritis patients where the immune response is protective and compartmentalized. We compared and correlated the cell-cycle analysis and antigen-induced apoptosis in normal and patients’ peripheral blood mononuclear cells (PBMCs) and patients’ pleural fluid mononuclear cells (PFMCs). In cell-cycle analysis, PFMCs showed good mitotic response with PPD and MTB antigens where 10% and 7% of resting cells entered the S and G2/M phases of cell cycle, respectively. This antigen-induced proliferation of PFMCs correlated well with the lymphocyte transformation test (LTT) results. On the other hand, PFMCs also showed 21% of spontaneous apoptosis, which further increased to 43%, by induction with known apoptotic agent like Dexamethasone (DEX) and the mycobacterial antigens PPD and MTB. Further we demonstrated by anti-CD3 induction experiments that prior activation of cells is prerequisite for them to undergo apoptosis. Our results showed that PPD and MTB antigens induced both cell proliferation and apoptosis in PFMCs, which were pre-sensitized to mycobacterial antigens in vivo. Thus the dual-signal phenomenon was operative against these antigens in tuberculous pleuritis. We also demonstrated that the activated cells are more predisposed to apoptosis.