ALVEOLAR MACROPHAGES AS ACCESSORY CELLS FOR HUMAN GAMMA-DELTA T-CELLSACTIVATED BY MYCOBACTERIUM-TUBERCULOSIS

Alveolar macrophages form the first line of defense against inhaled dr oplets containing Mycobacterium tuberculosis by controlling mycobacter ial growth and regulating T cell responses. CD4(+) and gamma delta T c ells, two major T cell subsets activated by M. tuberculosis, require a ccessory cells for activation. However, the ability of alveolar macrop hages to function as accessory cells for T cell activation remains con troversial. We sought to determine the ability of alveolar macrophages to serve as accessory cells for resting (HLA-DR(-), IL-2R(-)) and act ivated (HLA-DR(+), IL-2R(+)) gamma delta T cells in response to M. tub erculosis and its Ag, and to compare accessory cell function for gamma delta T cells of alveolar macrophages and blood monocytes obtained fr om the same donor. Alveolar macrophages were found to serve as accesso ry cells for both resting and activated gamma delta T cells in respons e to M. tuberculosis Ag. At high alveolar macrophage to T cell ratios (>3:1), however, expansion of resting gamma delta T cells was inhibite d by alveolar macrophages. The inhibition of resting gamma delta T cel ls by alveolar macrophages was dose-dependent, required their presence during the first 24 h, and was partially overcome by IL-2. Alveolar m acrophages did not inhibit activated gamma delta T cells even at high accessory cell to T cell ratios, and alveolar macrophages functioned a s well as monocytes as accessory cells. Monocytes were not inhibitory for either resting or activated gamma delta T cells. These findings su pport the following model. In the normal alveolus the alveolar macroph age to T cell ratio is greater than or equal to 9:1, and therefore the threshold for resting gamma delta T cell activation is likely to be h igh. Once a nonspecific inflammatory response occurs, such as after in vasion by M. tuberculosis, this ratio is altered, favoring gamma delta T cell activation by alveolar macrophages.