CD4(-CELL ASSOCIATED CYTOKINE GENE-EXPRESSION DURING EXPERIMENTAL-INFECTION WITH LISTERIA-MONOCYTOGENES - THE MESSENGER-RNA PHENOTYPE OF GRANULOMA-FORMATION() T)

In murine listeriosis, elimination of bacteria and immunity to re-infe ction critically depend on Thy1(+)CD4(-)cells, while cell-mediated inf lammatory phenomena like delayed-type hypersensitivity and granuloma f ormation are mediated by CD4(+) T cells. In an attempt to correlate T cell phenotype and function with a particular set of cytokines produce d in vivo, we examined the cytokine gene expression profile associated with the presence or absence of CD4(+) and/or CD8(+) cells in the liv ers of mice during experimental infection with Listeria monocytogenes. T cell subset depletion was achieved by i.p. administration of satura ting amounts of the appropriate mAbs, and mRNA detection was carried o ut using a qualitative and semi-quantitative polymerase chain reaction -based mRNA amplification protocol. In both primary and secondary infe ction, the presence of CD4(+) cells was a prerequisite for granuloma f ormation, and was found to be closely associated with mRNA expression for IL-2, IL-3 and IL-4, a 5-fold increase in expression of tumor necr osis factor (TNF)-alpha and granulocyte macrophage colony stimulating factor, and a 25-fold increase in expression of IFN-gamma and TNF-beta mRNAs, suggesting a role for these cytokines in granuloma formation. In striking contrast, depletion of CD8(+) cells did not result in redu ced mRNA expression for any one of the cytokines studied, implying tha t CD8(+) T cell mediated cure and prevention of listeriosis may operat e via qualitatively distinct mechanisms.