Function and distribution of thymus-dependent lymphocyte subsets involved in resistance to experimental pulmonary tuberculosis

Abstract

The adoptive transfer technique in a guinea pig model of pulmonary tuberculosis was used to analyze the function of thymus dependent lymphocytes involved in delayed hypersensitivity and resistance to pulmonary tuberculosis. The immunological spectrum of thymus dependent lymphocytes was expanded by introducing Mycobacterium tuberculosis H37Rv through two different routes, i.e. aerosol/pulmonary and intravenous. Using flowcytometric analysis, the study revealed a marked difference in the distribution of thymus dependent lymphocytes in two lymphocytic organs, the bronchotracheal lymph nodes and the spleen from each route of infection. Aerosol infection yielded more T lymphocytes, with predominance of the CD4 subset, in the bronchotracheal lymph nodes, while intravenous infection caused predominance of the CD4 subset in the spleen. This correlated with the ability to enhance resistance against pulmonary tuberculosis through the adoptive transfer technique in recipient guinea pigs. On the other hand, aerosol infected animals showed fewer CD8 and B cells in the circulation than their intravenous infected counterparts which, in turn, correlated directly with the ability to exhibit a delayed hypersensitivity reaction. The state of protein deprivation caused decreased expression of delayed hypersensitivity reactions and sequestration of the lymphocytes in the lymphoid organs. However, the protein deficient animals were also shown to have more enhanced resistance to pulmonary tuberculosis after receiving the donor immune lymphocytes. Protein deprivation manifested histologically as decreased cell size, a a more miliary pattern of lung tubercles, less collagenization in the granulomata formed and, therefore, less destruction of lung tissue. Measurement of IL-2 and IL-4, and the degree of mitogen and antigen induced proliferation did not show a clear correlation as contributory factors to the resistance against pulmonary tuberculosis in the guinea pigs. A significant enhancement of resistance was observed when cells were transferred intraperitoneally as opposed to subcutaneously, regardless of the nutritional status of the recipient animals. Through immunohistological labelling techniques and electron-microscopy, thymus dependent lymphocytes were visualized, as preliminary ground-work to further understand the mechanism of resistance against pulmonary tuberculosis in the guinea pig model.