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Published ahead of print on October 6, 2005, doi:10.1164/rccm.200503-411OC

Am. J. Respir. Crit. Care Med., Volume 173, Number 2, January 2006, 238-245

A more recent version of this article appeared on January 15, 2006
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Submitted on March 15, 2005
Accepted on October 6, 2005

Myobacterium tuberculosis Growth Control by Lung Macrophages and CD8 Cells from Patient Contacts

Claudia Carranza1, Esmeralda Juarez1, Martha Torres1, Jerrold J Ellner2, Eduardo Sada1, and Stephan K Schwander2*

1 Department of Microbiology, Instituto Nacional de Enfermedades Respiratorias (INER), Mexico City, Mexico, 2 Department of Medicine and Center for Emerging Pathogens, University of Medicine and Dentistry of New Jersey (UMDNJ), Newark, NJ, USA

* To whom correspondence should be addressed. E-mail: schwansk{at}umdnj.edu.

Rationale Healthy household contacts (HHC) of patients with active pulmonary tuberculosis are exposed aerogenically to Mycobacterium tuberculosis (M.tb) thus permitting the study of protective local immunity. Objectives To assess alveolar macrophage (AM) and autologous blood CD4 and CD8 T cell mediated M.tb growth control in HHC and healthy unexposed community controls (CC). Methods AM were infected with M.tb strains H37Ra and H37Rv at multiplicities of infection (MOI) 0.1 and 1, and M.tb colony forming units evaluated on days 1, 4, and 7. Main Results CD8 T cells from HHC in 1:1 cocultures with AM significantly (p<0.05) increased M.tb growth control by AM. In CC, no detectable contribution of CD8 T cells to M.tb growth control was observed. Neither in HHC nor in CC did CD4 T cells increase M.tb growth control. Interferon gamma (IFN-{gamma}), nitric oxide (NO) and tumor necrosis factor (TNF-{alpha}) were determined as potential mediators of M.tb growth control in AM, and AM/CD8 and AM/CD4 cocultures. IFN-{gamma} production in AM/CD4 was two-fold higher than that in AM/CD8 cultures in both HHC and CC (p<0.05). NO production from AM of HHC increased on days 4 and 7 and was undetectable in AM from CC. IFN-{gamma} and NO concentrations and M.tb growth control were not correlated. TNF-{alpha} levels were significantly increased in AM/CD8 from HHC compared to AM/CD8 from CC (p<0.05). Conclusion Aerogenic exposure to M.tb in HHC leads to expansion of M.tb specific effector CD8 T cells that limit M.tb growth in autologous AM.
Key words: Mycobacterium tuberculosis; T-Lymphocytes, Effector, Macrophages, Alveolar; Interferon Type II; nitric oxide.




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