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

In murine listeriosls, elimination of bacteria and immunityto re-infection critically depend on Thy-1⁺ CM^– cells,while cell-mediated inflammatory phenomena like delayed-typehypersensltlvlty and granuloma formation are mediated by CD4⁺T cells. In an attempt to correlate T cell phenotype and functionwith a particular set of cytokines produced in vivo, we examinedthe cytokine gene expression profile associated with the presenceor absence of CD4⁺ and/or CD8⁺ cells in the livers of mice duringexperimental infection with Usterta monocytogenes. T cell subsetdepletion was achieved by l.p. administration of saturatingamounts of the appropriate mAbs, and mRNA detection was carriedout using a qualitative and semi-quantitative polymerase chainreaction-based mRNA amplification protocol. In both primaryand secondary infection, the presence of CD4⁺ cells was a prerequisitefor granuloma formation, and was found to be closely associatedwith mRNA expression for IL-2, IL-3 and IL-4, a 5-fold increasein expression of tumor necrosis factor (TNF)- and granulocytemacrophage colony stimulating factor, and a 25-fold increasein expression of IFN- and TNF-ß mRNAs, suggestinga role for these cytokines in granuloma formation. In strikingcontrast, depletion of CD8⁺ cells did not result in reducedmRNA expression for any one of the cytokines studied, Implyingthat CD8⁺ T cell mediated cure and prevention of listerlosismay operate via qualitatively distinct mechanisms.