CD4+lymphocyte responses to pulmonary infection with Mycobacterium tuberculosis in naive and vaccinated BALB/c mice

Setting: Local CD4+ lymphocyte responses are critical in determining the fate of infection with Mycobacterium tuberculosis. Objective: To evaluate the lung and regional lymph node CD4+ lymphocyte responses to pulmonary infection with M. tuberculosis H37Rv in BALB/c mice, with and without prior vaccination with M. bovis Bacille Calmette-Guerin (BCG). Design: Lung and lung-associated lymph node (LALN) CD4+ lymphocytes were isolated from BALB/c mice infected with low dose M. tuberculosis H37Rv by the intratracheal route in BCG-vaccinated and unvaccinated animals, and cytokine responses assessed in vitro. Results: CD4+ lymphocytes increased in both the lung and LALN by 21 days after infection, and elicited production of interferon (IFN)-gamma was upregulated in the lymphocytes of the infected animals. Only low levels of interleukin (IL)-4 and IL-10 were elicited from the lung. The IFN-gamma response from both sites was facilitated in the previously vaccinated animals. Conclusion: In this model of low dose inoculation of M. tuberculosis in the lung, BALB/c mice respond with a Th1-biased CD4+ lymphocyte response, which is accentuated in animals previously vaccinated with BCG. (C) 2001 Harcourt Publishers Ltd.