| First Author | Combe CL | Year | 2006 |
| Journal | Proc Natl Acad Sci U S A | Volume | 103 |
| Issue | 17 | Pages | 6635-40 |
| PubMed ID | 16614074 | Mgi Jnum | J:109105 |
| Mgi Id | MGI:3625777 | Doi | 10.1073/pnas.0506180103 |
| Citation | Combe CL, et al. (2006) Lack of IL-15 results in the suboptimal priming of CD4+ T cell response against an intracellular parasite. Proc Natl Acad Sci U S A 103(17):6635-40 |
| abstractText | IFN-gamma-producing CD4+ T cells, although important for protection against acute Toxoplasma gondii infection, can cause gut pathology, which may prove to be detrimental for host survival. Here we show that mice lacking IL-15 gene develop a down-regulated IFN-gamma-producing CD4+ T cell response against the parasite, which leads to a reduction in gut necrosis and increased level of survival against infection. Moreover, transfer of immune CD4+ T cells from WT to IL-15-/- mice reversed inhibition of gut pathology and caused mortality equivalent to levels of parental WT mice. Down-regulated CD4+ T cell response in the absence of IL-15, manifested as reduced antigen-specific proliferation, was due to defective priming of the T cell subset by dendritic cells (DCs) of these animals. When stimulated with antigen-pulsed DCs from WT mice, CD4+ T cells from IL-15-/- mice were primed optimally, and robust proliferation of these cells was observed. A defect in the DCs of knockout mice was further confirmed by their reduced ability to produce IL-12 upon stimulation with Toxoplasma lysate antigen. Addition of exogenous IL-15 to DC cultures from knockout mice led to increased IL-12 production by these cells and restored their ability to prime an optimal parasite-specific CD4+ T cell response. To our knowledge, this is the first demonstration of the role of IL-15 in the development of CD4+ T cell immunity against an intracellular pathogen. Furthermore, based on these observations, targeting of IL-15 should have a beneficial effect on individuals suffering from CD4+ T cell-mediated autoimmune diseases. |
