Interleukin-18-related genes are induced during the contraction phase but do not play major roles in regulating the dynamics or function of the T-cell response to Listeria monocytogenes infection.
Proinflammatory cytokines, such as gamma interferon (IFN-gamma), impact aspects of T-cell responses after infection, including expansion, contraction, and memory formation. Interleukin-18 (IL-18) functions as a proinflammatory cytokine by stimulating the production of IFN-gamma from multiple cell types and accentuating the development of Th1 CD4 T-cell responses. Focused microarray analyses revealed upregulation of IL-18 and IL-18 receptor genes in CD8 T cells during the contraction phase. Based on these findings we investigated if and how signaling through the IL-18 receptor influences the development and kinetics of antigen (Ag)-specific CD8 and CD4 T-cell responses following infection. IL-18Ralpha(-/-) and IL-18(-/-) mice developed frequencies and total numbers of Ag-specific CD8 T cells after Listeria monocytogenes infection that were similar to those of wild-type C57BL/6 mice. The kinetics of expansion, contraction, and memory CD8 T-cell maintenance were also similar. When IL-18Ralpha deficiency was isolated to Ag-specific CD8 T cells, the kinetics of the expansion and contraction phases were also normal. These basic findings were confirmed by examining the response to vaccinia virus infection. In contrast, the expansion of Ag-specific CD4 T cells was slightly curtailed by the absence of IL-18Ralpha; however, contraction and the maintenance of memory were not altered. Importantly, both memory Ag-specific CD8 and CD4 T cells generated in the absence of IL-18Ralpha expanded appropriately after secondary antigen exposure and were protective, indicating that signaling through the IL-18 receptor is not required for normal T-cell response kinetics and survival of immunized mice challenged with a lethal L. monocytogenes infection.
Haring
Jodie S
JS
Department of Microbiology, 3-512 BSB, University of Iowa, 51 Newton Road, Iowa City, IA 52242, USA.
Harty
John T
JT
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000172:deficiency / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053724:Receptors, Interleukin-18 / Q000172:deficiency / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D020382:Interleukin-18; D053724:Receptors, Interleukin-18