Cytokine production and cytotoxicity mediated by CD4+ T cells from healthy subjects vaccinated with Mycobacterium bovis BCG and from pulmonary tuberculosis patients.

In tuberculosis, T cells are responsible for protection but also the pathology caused by inflammatory responses. Most T cells activated in response to Mycobacterium tuberculosis express the CD4 phenotype, and are divided into Th1 and Th2 subsets depending on the types of cytokines produced. Th1 cells protect against most intracellular infections including tuberculosis. To study the Th1 and Th2 profiles against M. tuberculosis antigens, we established CD4+ T cell clones from the peripheral blood mononuclear cells of healthy subjects vaccinated with Mycobacterium bovis BCG and of pulmonary tuberculosis patients. When tested for cytokine production in response to mycobacterial antigens and defined epitopes (i.e., whole killed M. tuberculosis, a 65-kDa heat shock protein, and synthetic peptides) the T cell clones produced cytokines typical of Th1 cells: interleukin 2, interferon-gamma, and granulocyte-macrophage colony-stimulating factor. The same T cells also had cytotoxic activity against antigen-pulsed macrophages. We propose that activation of macrophages by interferon-gamma and killing of the pathogen-laden macrophages by cytotoxic T cells may contribute to protection. However, the same mechanisms may also activate the release of soluble mediators responsible for inflammatory responses seen in tuberculosis granulomas.