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.