Overexpression of IL-21 promotes massive CD8+ memory T cell accumulation.
The ability of IL-21 to promote in vitro T cell survival led us to investigate its biological activity in vivo. We report that overexpression of IL-21 in transgenic mice drives CD8(+) memory T cell accumulation with a concomitant reduction in naive T cell numbers. These memory T cells are functional, given their ability to rapidly produce IFN-gamma and proliferate following stimulation. Since the homeostasis of naive and memory T cells is controlled by cytokines, we evaluated whether IL-21 influences cytokine receptor expression. We show that IL-21 inhibits IL-7R expression on naive T cells in vitro, suggesting impaired IL-7-mediated naive T cell survival in IL-21-transgenic mice. In contrast, IL-7R expression on CD4(+) memory T cells is not affected, allowing their IL-7-dependent survival in IL-21-transgenic mice. Although IL-21 decreases IL-7R expression on CD8(+) memory T cells, this has no impact on their survival since their maintenance in the T cell pool is IL-7-independent. Rather, we demonstrate that CD8(+) memory T cells are receptive to IL-21 survival signals allowing for their accumulation in IL-21-transgenic mice. This study identifies new roles for IL-21 in T cell homeostasis and in the regulation of T cell responses to cytokines.
Allard
Eve-Line
EL
Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Canada.
Hardy
Marie-Pierre
MP
Leignadier
Julie
J
Marquis
Miriam
M
Rooney
Julie
J
Lehoux
Dario
D
Labrecque
Nathalie
N
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D007156:Immunologic Memory; D015851:Interleukin-7 / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D020395:Receptors, Interleukin-7 / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D000098546:Interleukin-21
D015851:Interleukin-7; D007378:Interleukins; D020395:Receptors, Interleukin-7; D000098546:Interleukin-21