Differences in the ability to generate type 1 T helper cells need not determine differences in the ability to resist Mycobacterium tuberculosis infection among mouse strains.

摘要

BACKGROUND: C57BL/6 (B6) and BALB/c mice are considerably more resistant to infection with Mycobacterium tuberculosis than DBA/2 mice. METHODS: To determine whether the difference in resistance is because DBA/2 mice generate a type 1 T helper (Th1) immune response of lower magnitude, the Th1 response to airborne infection of mice of all 3 strains was measured in terms of the number of interferon (IFN)-gamma-producing CD4 and CD8 T cells generated. RESULTS: Despite the superior resistance of BALB/c mice compared with DBA/2 mice, both strains generated a similarly low number of Th1 cells. On the other hand, B6 mice, despite being approximately equal in resistance compared with BALB/c mice, generated a much larger number of Th1 cells. In DBA/2 mice, a higher level of lung infection was associated with larger numbers of M. tuberculosis bacilli in individual macrophages at sites of infection, indicating lower levels of macrophage mycobacteriostatic function. Despite this, infected macrophages from DBA/2 mice stained positive for nitric oxide synthase type 2 (NOS2) by immunocytochemistry as intensely as did infected macrophages from B6 and BALB/c mice, indicating the acquisition of NOS2-dependent mycobacteriostatic function in all cases. CONCLUSION: The ability to generate a large number of Th1 cells need not determine the ability to resist M. tuberculosis infection.