Interleukin-15 interactions with interleukin-15 receptor complexes: characterization and species specificity.

Interleukin (IL-) 2 and IL-15 share the IL-2 receptor betagamma c subunits (IL-2Rbetagamma c) but have specific, unique alpha receptor subunits. We studied species specificity of human (hu), simian (si), and mouse (mu) IL-15 and found that hu and si IL-15 behaved similarly in all systems investigated. Hu and mu IL-15 bound hu or mu IL-15Ralpha with equal high affinity in the presence or absence of IL-2Rbetagamma c and exhibited similar proliferative activities on cells containing all three subunits.

Lung epithelial barrier function and wound healing are decreased by IL-4 and IL-13 and enhanced by IFN-gamma.

To understand the effects of cytokines on epithelial cells in asthma, we have investigated the effects of interleukin (IL)-4, IL-13, and interferon (IFN)-gamma on barrier function and wound healing in Calu-3 human lung epithelial cells. IL-4 and IL-13 treatment of Calu-3 cells grown on Transwell filters resulted in a 70-75% decrease in barrier function as assessed by electrophysiological and [(14)C]mannitol flux measurements. In contrast, IFN-gamma enhanced barrier function threefold using these same parameters.

Interferon-gamma decreases barrier function in T84 cells by reducing ZO-1 levels and disrupting apical actin.

The effects of interferon-gamma (IFN-gamma) on tight junctions in T84 human intestinal epithelial cells were investigated. Treatment of T84 cells with IFN-gamma caused a dose- and time-dependent increase in monolayer permeability as assessed by transepithelial electrical resistance measurements. Examination of specific proteins associated with tight junctions by immunoblotting and confocal microscopy revealed changes in the expression levels and localization of some of these proteins after exposure of the cells to IFN-gamma.

Interleukin-15 up-regulates interleukin-2 receptor alpha chain but down-regulates its own high-affinity binding sites on human T and B cells.

The cytokines interleukin (IL)-2 and IL-15 share many biological activities as a consequence of their utilization of the beta and gamma chains of the IL-2 receptor. However, each cytokine binds to a specific receptor alpha chain; IL-2 with low affinity and IL-15 with high affinity. Here, we demonstrate that IL-15, like IL-2, up-regulates expression of IL-2R alpha on human T and B cells, but rapidly down-regulates IL-15 high-affinity binding sites, which represent IL-15R alpha.

Functional characterization of the human interleukin-15 receptor alpha chain and close linkage of IL15RA and IL2RA genes.

Interleukins-2 and -15 (IL-2 and IL-15) are cytokines with overlapping but distinct biological effects. Their receptors share two subunits (the IL-2R beta and -gamma chains) that are essential for signal transduction. The IL-2 receptor requires an additional IL-2-specific alpha subunit for high affinity IL-2 binding.

Characterization of B-cell lines established from two X-linked severe combined immunodeficiency patients: interleukin-15 binds to the B cells but is not internalized efficiently.

X-linked severe combined immunodeficiency (XSCID) is characterized by absent or profoundly reduced numbers of T cells and normal numbers of B cells in the circulation. Affected patients have mutations of the interleukin-2 (IL-2) receptor gamma chain gene. Using Epstein-Barr virus-transformed B-lymphoblastoid cell lines (B-LCLs) established from two unrelated XSCID patients, we could show that neither expressed the IL-2 receptor gamma chain on the cell surface.

Identification and cloning of a novel IL-15 binding protein that is structurally related to the alpha chain of the IL-2 receptor.

Interleukin-15 (IL-15) is a novel cytokine of the four-helix bundle family which shares many biological activities with IL-2, probably due to its interaction with the IL-2 receptor beta and gamma (IL-2R beta and gamma c) chains. We report here the characterization and molecular cloning of a distinct murine IL-15R alpha chain. IL-15R alpha alone displays an affinity of binding for IL-15 equivalent to that of the heterotrimeric IL-2R for IL-2.

Interleukin 15 and its receptor.

Interleukin 15 (IL-15) is a member of the four-helix bundle cytokine family that shares many in vitro biological activities with IL-2. Previous work demonstrated that IL-15 utilizes the beta and gamma chains of the IL-2 receptor (IL-2R), and that these are essential for IL-15-mediated signal transduction. However, several lines of evidence indicated the existence of an additional, IL-15-specific receptor component.

Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor.

Interleukin 15 (IL-15) is a novel cytokine that has recently been cloned and expressed. Whereas it has no sequence homology with IL-2, IL-15 interacts with components of the IL-2 receptor (IL-2R). In the present study we performed a functional analysis of recombinant IL-15 on phenotypically and functionally distinct populations of highly purified human natural killer (NK) cells.

Utilization of the beta and gamma chains of the IL-2 receptor by the novel cytokine IL-15.

We have recently cloned a novel cytokine, IL-15, with shared bioactivities but no sequence homology with IL-2. We found high affinity IL-15 binding to many cell types, including cells of non-lymphoid origin. Analysis of IL-15 interaction with subunits of the IL-2 receptor (IL-2R) revealed that the alpha subunit was not involved in IL-15 binding.

Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor.

A cytokine was identified that stimulated the proliferation of T lymphocytes, and a complementary DNA clone encoding this new T cell growth factor was isolated. The cytokine, designated interleukin-15 (IL-15), is produced by a wide variety of cells and tissues and shares many biological properties with IL-2. Monoclonal antibodies to the beta chain of the IL-2 receptor inhibited the biological activity of IL-15, and IL-15 competed for binding with IL-2, indicating that IL-15 uses components of the IL-2 receptor.