Abstract
Previous in vitro studies of the cellular immune response to mycobacteria have used live or dead avirulent organisms or purified products of Mycobacterium tuberculosis as the antigen source. The use of live virulent mycobacteria may provide a more useful model of human immunity to M. tuberculosis. This in vitro system closely approximates some of the cellular events occurring in a tuberculous granuloma. Peripheral blood mononuclear cells were obtained from individuals representing three phases of mycobacterial immunity, i.e. naive, B C G -immunized, and tuberculosis patients. Monocytes were isolated and given a very low level infection with M. tuberculosis H37Rv, and nonadherent cells added back for a seven day coculture. Clonal expansion of the T cell subpopulations was assessed by flow cytometry using monoclonal antibodies to CD3, CD4, CD8, TCRα[beta], TCR[gamma]δ, and CD28. Shifts in T cell phenotypes, including TCR[gamma]δ+ T cell expansion, were observed in response to M. tuberculosis-infected macrophages. The cellular dynamics reflected the nature of the sensitizing experience and the degree of cellular reactivity as measured by tuberculin skin test and lymphoproliferation. Granulomatous inflammation in tuberculosis also involves T cell- and monocyte-derived polypeptide signals which stimulate and modulate lymphocyte responses, and recruit and activate inflammatory cells. Induction of cytokine expression within this model was examined at optimal time points during culture. Using polymerase chain reaction technology, gene expression at the mRNA level for the cytokines IL-1[beta], IL-2, TNFα, and IFN[gamma] was quantitated in cells from the in vitro infection system. Expression of cytokine mRNA varied with the clinical status of the cell donor and the nature of the antigenic stimulus. These data were correlated with the level of anti-mycobacterial immunity in the donor, and should contribute to a better understanding of the cytokine networks involved in T cell activation in tuberculosis.
Johnson, Barbara Jane (1992). The coordination of the leukocyte response to Mycobacterium tuberculosis-infected macrophages. Texas A&M University. Texas A&M University. Libraries. Available electronically from
https : / /hdl .handle .net /1969 .1 /DISSERTATIONS -1420107.