CYTOKINE PRODUCTION AND CYTOTOXICITY MEDIATED BY CD4(-CELLS FROM HEALTHY-SUBJECTS VACCINATED WITH MYCOBACTERIUM-BOVIS BCG AND FROM PULMONARY TUBERCULOSIS PATIENTS() T)

In tuberculosis, T cells are responsible for protection but also the p athology caused by inflammatory responses. Most T cells activated in r esponse to Mycobacterium tuberculosis express the CD4 phenotype, and a re divided into Th1 and Th2 subsets depending on the types of cytokine s produced. Th1 cells protect against most intracellular infections in cluding tuberculosis. To study the Th1 and Th2 profiles against M. tub erculosis antigens, we established CD4+ T cell clones from the periphe ral blood mononuclear cells of healthy subjects vaccinated with Mycoba cterium bovis BCG and of pulmonary tuberculosis patients. When tested for cytokine production in response to mycobacterial antigens and defi ned epitopes (i.e., whole killed M. tuberculosis, a 65-kDa heal 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 cytot oxic activity against antigen-pulsed macrophages. We propose that acti vation of macrophages by interferon-gamma and killing of the pathogen- laden macrophages by cytotoxic T cells may contribute to protection. H owever, the same mechanisms may also activate the release of soluble m ediators responsible for inflammatory responses seen in tuberculosis g ranulomas.