Modulation of dendritic cell regulatory CD4+ T cells

The consequences of interactions between dendric cells (DCs) and either naive CD4(+) T cells or regulatory CD4(+)CD25(+) T cells on the expression of proinflammatory IL-6 and anti-inflammatory IL-10 in DC were examined over a period of 12 h, spanning the time frame during which stable T cell-DC interactions shape the development of tolerance and immunity in vivo. We demonstrate that the basal production of IL-6 and IL-10, which is initiated following DC stimulation with LPS, is modified in distinctly different ways by interaction with the two T cell populations. Naive CD4(+) T cells skew DC cytokine production toward IL-6 and suppress IL-10, whereas CD4(+)CD25(+) T cells have the opposite effect. CD8 T cells or memory CD4(+) T cells do not influence basal cytokine production by stimulated DC. The effect of CD4(+)CD25(+) T cells is dominant in coculture with naive CD4(+) T cells as long as inflammatory LPS is absent; the addition of LPS abrogates the suppression of IL-6. However, the modulating influence of CD4(+)CD25(+) T cells remains evident in the enhancement of IL-10 production. Thus, mutual interactions between DC and CD4(+) T cell subpopulations following contact with pathogens are likely to influence the strength and quality of incipient immune responses in the local microenvironment.