A regulatory T cell-dependent novel function of CD25 (IL-2Ralpha) controlling memory CD8(+) T cell homeostasis.
A massive systemic expansion of CD8(+) memory T (T(M)) cells and a remarkable increase in circulating IL-2 were observed only in IL-2Ralpha (CD25) knockout (KO) mice but not in IL-2 KO and scurfy mice, although all three mutants lack regulatory T (Treg) cells. However, both phenotypes were suppressed by the transfer of Treg cells. The data presented indicate that Treg cell deficiency drives naive T cells to T(M) cells. The lack of high-affinity IL-2R in IL-2Ralpha KO mice increases circulating IL-2 that is then preferentially used by CD8(+) T(M) cells through its abundant low-affinity IL-2R, resulting in systemic CD8(+) T(M) cell dominance. Our study demonstrates the critical control of CD8(+) T(M) cell homeostasis by a Treg cell-dependent novel function of CD25 and resolves its mechanism of action.
Sharma
Rahul
R
Division of Rheumatology and Immunology, Department of Internal Medicine, University of Virginia, Charlottesville, VA 22908, USA.
Zheng
Lingjie
L
Deshmukh
Umesh S
US
Jarjour
Wael N
WN
Sung
Sun-Sang J
SS
Fu
Shu Man
SM
Ju
Shyr-Te
ST
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D006706:Homeostasis / Q000276:immunology*; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000097:blood / Q000502:physiology; D053645:Interleukin-2 Receptor alpha Subunit / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000502:physiology* / Q000637:transplantation
D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit