Mycobacterial antigens induce apoptosis in human purified protein derivative-specific alphabeta T lymphocytes in a concentration-dependent manner.
The morbidity and lethality of tuberculosis is partially the result of an ineffective delayed-type hypersensitivity reaction which causes caseating granulomas in the lung and other organs. Recently we showed that during caseation besides macrophages numerous Fas+ FasL+ lymphocytes undergo apoptosis and postulated that this phenomenon may be due to activation-induced cell death (AICD) as a consequence of T-lymphocyte reactivation via bacillary antigens. As purified protein derivative of Mycobacterium tuberculosis (Mtb-PPD) provokes caseation in tuberculosis patients, the question arose as to whether bacillary antigens are responsible for AICD within caseous areas. In the present study Mtb-PPD-specific T helper 1 (Th1)-differentiated T lymphocytes were generated in vitro. Reactivation of these cells with Mtb-PPD resulted in a concentration-dependent hyporesponsiveness, which was due to an increase in apoptosis of gammadelta+, alphabeta+ CD4+ as well as alphabeta+ CD8+ T lymphocytes as assessed by the demonstration of the apoptosis-associated mitochondrial membrane protein 7A6 and DNA fragmentation. Blocking experiments demonstrated that Mtb-PPD antigens exploited the Fas/FasL system to induce apoptosis in Mtb-PPD-specific T lymphocytes. These results may support the hypothesis that in tubercle granulomas with caseation T lymphocytes undergo AICD following reactivation by bacillary antigens, thus contributing to the persistence of tuberculosis.
Soruri
Afsaneh
A
Department of Immunology, Georg August University Goettingen, Robert-Koch-Strasse 40, D-37075 Goettingen, Germany.
Schweyer
Stefan
S
Radzun
Heinz-Joachim
HJ
Fayyazi
Afshin
A
D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014373:Tuberculin / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D014373:Tuberculin