scholarly journals Inducible nitric oxide synthase in T cells regulates T cell death and immune memory

2004 ◽  
Vol 113 (12) ◽  
pp. 1734-1742 ◽  
Author(s):  
Monika Vig ◽  
Smita Srivastava ◽  
Usha Kandpal ◽  
Hadassah Sade ◽  
Virginia Lewis ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Immune Memory ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

scholarly journals αβ T Cell Receptor-positive Cells and Interferon-γ, but not Inducible Nitric Oxide Synthase, Are Critical for Granuloma Necrosis in a Mouse Model of Mycobacteria-induced Pulmonary Immunopathology

2001 ◽  
Vol 194 (12) ◽  
pp. 1847-1859 ◽  
Author(s):  
Stefan Ehlers ◽  
Jochen Benini ◽  
Heinz-Dieter Held ◽  
Christiane Roeck ◽  
Gottfried Alber ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
T Cell ◽  
Nitric Oxide Synthase ◽  
T Cell Receptor ◽  
Inducible Nitric Oxide Synthase ◽  
Bacterial Load ◽  
Cell Receptor ◽  
Ifn Γ ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The immunological basis of tuberculin-induced necrosis, known for more than a century as “Koch's phenomenon,” remains poorly understood. Aerosol infection in mice with the highly virulent Mycobacterium avium strain TMC724 causes progressive pulmonary pathology strongly resembling caseating necrosis in human patients with tuberculosis. To identify the cellular and molecular mediators causing this pathology, we infected C57BL/6 mice and mice selectively deficient in recombinase activating gene (RAG)-1, αβ T cell receptor (TCR), γδ TCR, CD4, CD8, β2-microglobulin, interferon (IFN)-γ, interleukin (IL)-10, IL-12p35, IL-12p35/p40, or iNOS with M. avium by aerosol and compared bacterial multiplication, histopathology, and respiratory physiology in these mice. The bacterial load in the lung was similarly high in all mouse groups. Pulmonary compliance, as a surrogate marker for granulomatous infiltrations in the lung, deteriorated to a similar extent in all groups of mice, except in αβ TCR-knockout (KO) and IL-12–KO mice in which compliance was higher, and in IFN-γ and inducible nitric oxide synthase–KO mice in which compliance was reduced faster. Progressive caseation of pulmonary granulomas never occurred in αβ TCR-KO, IL-12–KO, and IFN-γ–KO mice and was reduced in CD4-KO mice. In summary, αβ TCR+ cells and IFN-γ are essential for the development of mycobacteria-induced pulmonary caseous necrosis. In contrast, high mycobacterial load and extensive granulomatous infiltration per se are not sufficient to cause caseation, nor is granuloma necrosis linked to the induction of nitric oxide.

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