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Modulation of Dendritic Cell Function by Naive and Regulatory CD4⁺ T Cells¹

Division of Molecular Immunology, the Medical Research Council, National Institute for Medical Research, London, United Kingdom

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.

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