THE COURSE OF MYCOBACTERIUM-TUBERCULOSIS INFECTION IN THE LUNGS OF MICE LACKING EXPRESSION OF EITHER PERFORIN-MEDIATED OR GRANZYME-MEDIATEDCYTOLYTIC MECHANISMS

CD8 T cells have been shown to be protective against Mycobacterium tub erculosis infections in the mouse. These cells have been shown to be c ytolytic toward M. tuberculosis-infected cells and have also been show n to release the protective cytokine gamma interferon in response to m ycobacterial antigen. It has therefore been unclear how these cells me diate their protective response. To dissect this problem, we compared the courses of M. tuberculosis infections in control, perforin gene-kn ockout, and granzyme gene-knockout mice exposed by the realistic pulmo nary route. The inability to express either of these molecules limits the expression of the major lytic pathway but does not appear to influ ence the course of the infection or result in any discernible histolog ic differences. These data seem to rule against a lytic role for CD8 T cells in the lungs and hence tend to suggest instead that another typ e of mechanism, such as cytokine secretion by these cells, is their pr imary mode of action.