title: A regulatory T cell-dependent novel function of CD25 (IL-2Ralpha) controlling memory CD8(+) T cell homeostasis.
abstract: 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.
authors.affiliation: Division of Rheumatology and Immunology, Department of Internal Medicine, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Sharma
authors.forename: Lingjie
authors.initials: L
authors.lastname: Zheng
authors.forename: Umesh S
authors.initials: US
authors.lastname: Deshmukh
authors.forename: Wael N
authors.initials: WN
authors.lastname: Jarjour
authors.forename: Sun-Sang J
authors.initials: SS
authors.lastname: Sung
authors.forename: Shu Man
authors.initials: SM
authors.lastname: Fu
authors.forename: Shyr-Te
authors.initials: ST
authors.lastname: Ju
mesh_terms: 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
chemical_list: D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit