Document Type
Article
Publication Date
4-25-2006
Publication Title
Proceedings of the National Academy of Sciences of the United States of America
Department
Geisel School of Medicine
Abstract
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.
DOI
10.1073/pnas.0506180103
Original Citation
Combe CL, Moretto MM, Schwartzman JD, Gigley JP, Bzik DJ, Khan IA. 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. 2006 Apr 25;103(17):6635-40. doi: 10.1073/pnas.0506180103. Epub 2006 Apr 13. PMID: 16614074; PMCID: PMC1458934.
Dartmouth Digital Commons Citation
Combe, Crescent L.; Moretto, Magali M.; Schwartzman, Joseph D.; Gigley, Jason P.; Bzik, David J.; and Khan, Imtiaz A., "Lack of IL-15 Results in the Suboptimal Priming of CD4+ T Cell Response against an Intracellular Parasite" (2006). Dartmouth Scholarship. 1398.
https://digitalcommons.dartmouth.edu/facoa/1398
