Interleukin-15 differentially enhances the expression of interferon-γ and interleukin-4 in activated human (CD4+) T lymphocytes

In this study interleukin (IL)-15 was examined for its ability to modulate the expression of interferon-γ (IFN-γ) and IL-4 in activated human T lymphocytes. The effect of IL-15 was compared with IL-2 and IL-7, cytokines all known to use the IL-2 receptor γC chain. The results demonstrate that the extent of upregulation of IFN-γ and IL-4 mRNA was dependent on the applied cytokine (IL-2>IL-15>IL-7) and on the stimulatory signal. IFN-γ and IL-4 mRNAs were upregulated by IL-15 in concanavalin A- (twofold) and anti-CD3 plus anti-CD28- (fivefold) stimulated T lymphocytes. IFN-γ mRNA accumulation, but not IL-4 mRNA, was additively upregulated by IL-15 plus IL-7 (ninefold) in anti-CD3 stimulated T lymphocytes, and bypassed the requirement of CD28 signalling. Fluorescence-activated cell sorting (FACS) experiments demonstrated that IFN-γ mRNA was upregulated by IL-15 in both CD4+ and CD8+ T lymphocytes, whereas IL-4 mRNA accumulation predominantly occurred in CD4+ cells. Preincubation of highly purified CD4+ T lymphocytes during 7 days with IL-15 and/or IL-7, followed by activation, also showed enhanced IL-4 protein secretion, but predominantly upregulated IFN-γ protein. The net effect was a dramatically increased IFN-γ/IL-4 ratio. Taken together, IL-15 and IL-7 can act as costimulatory signals, which may favour a T helper 1 (Th1) immune response, particularly in the absence of sufficient CD28 costimulation

Granulocyte-macrophage colony-stimulating factor and the immune system

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multifunctional cytokine currently used for the reversal of neutropenia associated with cytotoxic chemotherapy, bone marrow and haemopoietic stem cell transplantation. GM-CSF also modulates the function of differentiated white blood cells. In the context of local inflammatory responses, GM-CSF stimulates macrophages for antimicrobial and antitumor effects. GM-CSF further enhances healing and repair by its actions on fibroblasts and epidermal cells. GM-CSF is the pivotal mediator of the maturation and function of dendritic cells, the most important cell type for the induction of primary T cell immune responses. GM-CSF may enhance antibody dependent cellular cytotoxicity (ADCC) in several cell types, and the generation and cytotoxicity of natural killer (NK) cells. On this basis, GM-CSF may be useful for inducing or augmenting antibody responses to antimicrobial vaccines, to enhance killing of intracellular microorganisms, to accelerate epidermal and mucosal wound healing, and to stimulate protective immunity against tumors

Interleukin-15 production at the early stage after oral infection with Listeria monocytogenes in mice

We previously reported that exogenous interleukin-15 (IL-15) induces proliferation and activation of intestinal intraepithelial lymphocytes (i-IEL) in naive mice. To investigate the ability of endogenous IL-15 to stimulate i-IEL in vivo, we monitored i-IEL and intestinal epithelial cells (i-EC) in mice after an oral infection with Listeria monocytogenes. Although the populations of αβ and γδ i-IEL were not significantly changed after the oral infection, the expression level of interferon-γ (IFN-γ) was increased both at transcriptional and protein levels, and a conversely marked decrease in interleukin-4 (IL-4) was detected in the i-IEL on day 1 after infection as compared with before infection. The T helper 1 (Th1)-biased response of i-IEL coincided with a peak response of IL-15 production in the i-EC after oral infection. These results suggested that IL-15 produced from i-EC may be at least partly involved in the stimulation of i-IEL to produce IFN-γ after oral infection with L. monocytogenes