Weijia Xia

lnterleukin-2 Promotes the Motility of Dendritic Cells and Their Accumulation in Lung and Skin

Dendritic cells (DC) play a critical role as antigen-presenting cells in vivo. It has previously been shown that DC accumulate in the lung in response to parenteral injections of IFN-gamma. In the current paper, we report that rat DC express the interleukin-2 receptor (IL-2R) alpha-chain (OX-39) and display enhanced motility in response to IL-2 in Boyden chamber and video time-lapse microscopy assays. Increased motility was specifically inhibited by pretreating DC with OX-39 (anti-IL-2R) but not OX-22 (anti-CD45RC), an isotype-matched murine monoclonal antibody. The intratracheal injection of IL-2 increased the number of OX-6+ dendritic cells located around pulmonary venules and in the lung interstitium. When IL-2 was injected into the footpad of the rat. DC were increased around dermal venules at 24 h. This effect was blocked by the parenteral injection of anti-OX-39. We conclude that IL-2 is a potent enhancer of DC motility and may cooperate with other T helper(h)-1 proinflammatory cytokines in attracting DC to sites of inflammation.

Interferon-Gamma and Tumor Necrosis Factor-Alpha Promote the Binding of Dendritic Cells to Fibronectin

Connective tissue dendritic accessory cells (DC) accumulate at sites of extracellular matrix (ECM) deposition. The adherence of DC to purified ECM proteins was examined. Splenic and pulmonary DC were purified from Lewis rats and incubated on slides coated with fibronectin (FN), laminin (LN), or collagen (COLL) types I, III and IV. In other experiments, DC were pre-incubated with selected proinflammatory cytokines (IL-1, IL-2, IFN-gamma, TNF-alpha) in order to determine their abilities to modulate cell adherence to ECM. Both splenic and pulmonary DC showed dose-dependent binding to FN that was inhibited by the synthetic peptide arg-gly-asp-ser. There was minimal DC binding to LN or COLL. Pretreating DC with IFN-gamma or TNF-alpha enhanced DC binding to FN but did not increase binding to LN or COLL. IL-1 and IL-2 had no demonstrable effect on DC binding to ECM. Our results suggest that FN is a critical ligand for DC in their binding to the ECM. IFN-gamma and TNF-alpha increase adherence of DC to FN and may promote their accumulation in the lung during inflammation.

Cytokine Administration Alters the Distribution of Activated Lymphocytes to the Lung

The effects of intraperitoneal injections of recombinant interleukin-1 alpha (IL-1; 250,000 U/day), interleukin-2 (IL-2; 50,000 units/day), interferon-gamma (IFN-gamma; 50,000 U/day) and tumor necrosis factor-alpha (TNF; 100,000 U/day), on the biodistribution of concanavalin A (Con A)-activated, indium-111-labeled lymphocytes were evaluated in BALB/c mice. Syngeneic spleen cells were activated for 48 h in medium with Con A (5 micrograms/ml) and maintained in culture for 72 h in IL-2 (1,000 U/ml). Groups of 12 mice were treated for 4 days with either one of the cytokines or saline. On day 4, mice received 10(7) lymphocytes (3-5 mu Ci) intravenously. Mice were sacrificed at 4 and 24 h following injection and the percent of administered dose per organ was determined. TNF and IL-1 produced a significant increase in lung uptake of radiolabeled lymphocytes at 4 and 24 h, whereas IL-2 and IFN-gamma decreased uptake at both time points. IL-1 increased uptake by liver at 4 and 24 h while IL-2 increased uptake only at 4 h. We conclude that the distribution of activated lymphocytes following adoptive transfer is altered by cytokines. This finding may have important implications for cell delivery during adoptive immunotherapy.