Distinct IL-2 receptor signaling pattern in CD4+CD25+ regulatory T cells

被引:227
作者
Bensinger, SJ
Walsh, PT
Zhang, JD
Carroll, M
Parsons, R
Rathmell, JC
Thompson, CB
Burchill, MA
Farrar, MA
Turka, LA
机构
[1] Univ Penn, Dept Med, Philadelphia, PA 19104 USA
[2] Columbia Univ, Dept Pathol & Med, New York, NY 10032 USA
[3] Univ Penn, Abramson Family Canc Res Inst, Dept Canc Biol, Philadelphia, PA 19104 USA
[4] Univ Penn, Abramson Family Canc Res Inst, Dept Med, Philadelphia, PA 19104 USA
[5] Univ Minnesota, Dept Lab Med & Pathol, Ctr Canc, Ctr Immunol, Minneapolis, MN 55455 USA
关键词
D O I
10.4049/jimmunol.172.9.5287
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Despite expression of the high-affinity IL-2R, CD4(+)CD25(+) regulatory T cells (Tregs) are hypoproliferative upon IL-2R stimulation in vitro. However the mechanisms by which CD4(+)CD25(+) T cells respond to IL-2 signals are undefined. In this report, we examine the cellular and molecular responses of CD4(+)CD25(+) Tregs to IL-2. IL-2R stimulation results in a G(1) cell cycle arrest, cellular enlargement and increased cellular survival of CD4(+)CD25(+) T cells. We find a distinct pattern of IL-2R signaling in which the Janus kinase/STAT pathway remains intact, whereas IL-2 does not activate downstream targets of phosphatidylinositol 3-kinase. Negative regulation of phosphatidylinositol 3-kinase signaling and IL-2-mediated proliferation of CD4(+)CD25(+) T cells is inversely associated with expression of the phosphatase and tensin homologue deleted on chromosome 10, PTEN.
引用
收藏
页码:5287 / 5296
页数:10
相关论文
共 44 条
[1]   Transduction of interleukin-2 antiapoptotic and proliferative signals via Akt protein kinase [J].
Ahmed, NN ;
Grimes, HL ;
Bellacosa, A ;
Chan, TO ;
Tsichlis, PN .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (08) :3627-3632
[2]   Homeostasis of peripheral CD4+ T cells:: IL-2Rα and IL-2 shape a population of regulatory cells that controls CD4+ T cell numbers [J].
Almeida, ARM ;
Legrand, N ;
Papiernik, M ;
Freitas, AA .
JOURNAL OF IMMUNOLOGY, 2002, 169 (09) :4850-4860
[3]   Phosphatidylinositol 3-kinase couples the interleukin-2 receptor to the cell cycle regulator E2F [J].
Brennan, P ;
Babbage, JW ;
Burgering, BMT ;
Groner, B ;
Reif, K ;
Cantrell, DA .
IMMUNITY, 1997, 7 (05) :679-689
[4]   Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery [J].
Datta, SR ;
Dudek, H ;
Tao, X ;
Masters, S ;
Fu, HA ;
Gotoh, Y ;
Greenberg, ME .
CELL, 1997, 91 (02) :231-241
[5]   Impaired Fas response and autoimmunity in Pten+/- mice [J].
Di Cristofano, A ;
Kotsi, P ;
Peng, YF ;
Cordon-Cardo, C ;
Elkon, KB ;
Pandolfi, PP .
SCIENCE, 1999, 285 (5436) :2122-2125
[6]   ANALYSIS OF GENE-EXPRESSION IN SINGLE LIVE NEURONS [J].
EBERWINE, J ;
YEH, H ;
MIYASHIRO, K ;
CAO, YX ;
NAIR, S ;
FINNELL, R ;
ZETTEL, M ;
COLEMAN, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (07) :3010-3014
[7]   CD4+CD25+ T cells facilitate the induction of T cell anergy [J].
Ermann, J ;
Szanya, V ;
Ford, GS ;
Paragas, V ;
Fathman, CG ;
Lejon, K .
JOURNAL OF IMMUNOLOGY, 2001, 167 (08) :4271-4275
[8]   Evidence that SHIP-1 contributes to phosphatidylinositol 3,4,5-trisphosphate metabolism in T lymphocytes and can regulate novel phosphoinositide 3-kinase effectors [J].
Freeburn, RW ;
Wright, KL ;
Burgess, SJ ;
Astoul, E ;
Cantrell, DA ;
Ward, SG .
JOURNAL OF IMMUNOLOGY, 2002, 169 (10) :5441-5450
[9]   Phosphoinositide 3-kinase in immunological systems [J].
Fruman, DA ;
Cantley, LC .
SEMINARS IN IMMUNOLOGY, 2002, 14 (01) :7-18
[10]   Signaling domains of the interleukin 2 receptor [J].
Gaffen, SL .
CYTOKINE, 2001, 14 (02) :63-77