CD4+ T cell associated cytokine gene expression during experimental infection with Listeria monocytogenes: the mRNA phenotype of granuloma formation.

Abstract

In murine listeriosis, elimination of bacteria and immunity to re-infection critically depend on Thy-1+CD4- cells, while cell-mediated inflammatory phenomena like delayed-type hypersensitivity and granuloma formation are mediated by CD4+ T cells. In an attempt to correlate T cell phenotype and function with a particular set of cytokines produced in vivo, we examined the cytokine gene expression profile associated with the presence or absence of CD4+ and/or CD8+ cells in the livers of mice during experimental infection with Listeria monocytogenes. T cell subset depletion was achieved by i.p. administration of saturating amounts of the appropriate mAbs, and mRNA detection was carried out using a qualitative and semi-quantitative polymerase chain reaction-based mRNA amplification protocol. In both primary and secondary infection, the presence of CD4+ cells was a prerequisite for granuloma formation, 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 necrosis 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 reduced mRNA expression for any one of the cytokines studied, implying that CD8+ T cell mediated cure and prevention of listeriosis may operate via qualitatively distinct mechanisms.