IL-4 induces differentiation and expansion of Th2 cytokine-producing eosinophils.

Innate effector cells that produce Th2-type cytokines are critical in Th2 cell-mediated immune responses. However, it is not known how these cells acquire the ability to produce Th2 cytokines. IL-4 is a potent inducer that directs differentiation of naive CD4(+) T cells into CD4(+) Th2 effector cells. To determine whether IL-4 can induce differentiation and expansion of Th2 cytokine-producing innate cells, we used mice whose il-4 gene was replaced by a knock-in green fluorescence protein (gfp) gene. We found that, directly ex vivo, IL-4 increased the number of GFP(+) cells in the airway and the lung tissue in an Ag-specific manner. The majority of GFP(+) cells were eosinophils, suggesting that IL-4 plays a pivotal role in expanding IL-4-producing eosinophils in vivo. IL-4-producing eosinophils showed some unique features compared with IL-4-producing CD4(+) T cells. They exhibited biallelic expression of the il-4 gene when stimulated and were more dominant IL-4- and IL-5-producing cells. Furthermore, we show that IL-4 drove bone marrow progenitor cells to differentiate into Th2 cytokine-producing eosinophils in vitro. These results strongly suggest IL-4 is a potent factor in directing bone marrow progenitor cells to differentiate into Th2 cytokine-producing eosinophils.

Survival and cell mediated immunity after burn injury in aged mice.

The elderly are less able to survive burn injury than young healthy individuals. Regardless of age, burn victims often succumb to secondary infections rather than the primary injury. Since immune responses diminish with age, it is likely that aged individuals are predisposed to a poor outcome by virtue of their weak immune system. Elevated production of macrophage-derived mediators, including interleukin-6 (IL-6), may lead to post-injury immunosuppression in young adults. Healthy aged individuals produce high circulating levels of these mediators; therefore, the combination of the age and burn trauma could further suppress immune responses and contribute to the rapid demise of aged burn patients. Herein, the effects of age and burn trauma using a murine scald injury model were examined. After injury, aged mice are less likely to survive, are unable to mount immune responses, and produce more IL-6 when compared to young adult mice given the same size injuries. Enhancing our understanding of the mechanisms responsible for regulating cell-mediated immune responses after injury could lead to the development of therapies designed to treat aged burn patients.