THE MESSENGER-RNA-PHENOTYPE OF GRANULOMA-FORMATION - CD4(-CELL-ASSOCIATED CYTOKINE GENE-EXPRESSION DURING PRIMARY MURINE LISTERIOSIS() T)

In murine listeriosis, elimination of bacteria and immunity to reinfec tion critically depend on Thy1(+) CD4(-) cells, while cell-mediated in flammatory phenomena such as DTH and granuloma formation are mostly me diated by CD4(+) T cells. In an attempt to correlate T cell phenotype and function with a particular set of cytokines produced, we examined the cytokine gene expression profile associated with the presence or a bsence of Thy1(+), CD4(+) and/or CD8(+) cells in the livers of mice du ring a primary infection with L. monocytogenes. The presence of CD4(+) cells was found to be closely associated with mRNA expression for IL- 2, IL-3 and IL-4, a 5-fold increase in expression of TNF-alpha and GM- CSF and a 25-fold increase in expression of IFN-gamma and TNF-beta mRN As, and temporally coincided with the development of granulomatous les ions. In vivo neutralization of TNF-alpha and, to a lesser extent, IFN -gamma resulted in abrogation of granuloma formation. A similar coil-e lation between the presence of CD8(+) cells and mRNA expression for an y one of the cytokines studied did not exist, pointing to a qualitativ ely different mechanism of CD8(+) T cell mediated sure of listeriosis.