Cutting edge:: OX40 inhibits TGF-β- and antigen-driven conversion of naive CD4 T cells into CD25+Foxp3+ T cells

被引:166
作者
So, Takanori [1 ]
Croft, Michael [1 ]
机构
[1] La Jolla Inst Allergy & Immunol, Div Mol Immunol, La Jolla, CA 92037 USA
关键词
D O I
10.4049/jimmunol.179.3.1427
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Naive CD4 T cells can develop into regulatory T cells by acquiring the transcription factor Foxp3. Combined signals from the TCR, CD28, IL-2R, and TGF-beta R promote Foxp3 expression in activated naive CD25(-) CD4 T cells. Here we show that OX40 (CD134) signaling inhibits TGF-beta-driven Foxp3 mRNA and suppresses the conversion of naive Ag-specific transgenic CD4 Tcells into CD25(+)Foxp3(+) T cells. These data identify OX40 as a negative regulator of Foxp3 and suggest that OX40 can concomitantly promote effector T cell generation while antagonizing the differentiation of adaptive Foxp3(+) regulatory T cells.
引用
收藏
页码:1427 / 1430
页数:4
相关论文
共 24 条
  • [1] In vivo instruction of suppressor commitment in naive T cells
    Apostolou, I
    von Boehmer, H
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 199 (10) : 1401 - 1408
  • [2] Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse
    Brunkow, ME
    Jeffery, EW
    Hjerrild, KA
    Paeper, B
    Clark, LB
    Yasayko, SA
    Wilkinson, JE
    Galas, D
    Ziegler, SF
    Ramsdell, F
    [J]. NATURE GENETICS, 2001, 27 (01) : 68 - 73
  • [3] Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3
    Chen, WJ
    Jin, WW
    Hardegen, N
    Lei, KJ
    Li, L
    Marinos, N
    McGrady, G
    Wahl, SM
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 198 (12) : 1875 - 1886
  • [4] Co-stimulatory members of the TNFR family: Keys to effective T-cell immunity?
    Croft, M
    [J]. NATURE REVIEWS IMMUNOLOGY, 2003, 3 (08) : 609 - 620
  • [5] Cutting edge:: IL-2 is essential for TGF-β-mediated induction of Foxp3+ T regulatory cells
    Davidson, Todd S.
    DiPaolo, Richard J.
    Andersson, John
    Shevach, Ethan M.
    [J]. JOURNAL OF IMMUNOLOGY, 2007, 178 (07) : 4022 - 4026
  • [6] Cutting edge:: TGF-β induces a regulatory phenotype in CD4+CD25- T cells through Foxp3 induction and down-regulation of Smad7
    Fantini, MC
    Becker, C
    Monteleone, G
    Pallone, F
    Galle, PR
    Neurath, MF
    [J]. JOURNAL OF IMMUNOLOGY, 2004, 172 (09) : 5149 - 5153
  • [7] Foxp3 Programs the Development and Function of CD4+CD25+ Regulatory T Cells (Reprinted from vol 4, pg 330-336, 2003)
    Fontenot, Jason D.
    Gavin, Marc A.
    Rudensky, Alexander Y.
    [J]. JOURNAL OF IMMUNOLOGY, 2017, 198 (03) : 986 - 992
  • [8] Gramaglia I, 1998, J IMMUNOL, V161, P6510
  • [9] The OX40 costimulatory receptor determines the development of CD4 memory by regulating primary clonal expansion
    Gramaglia, I
    Jember, A
    Pippig, SD
    Weinberg, AD
    Killeen, N
    Croft, M
    [J]. JOURNAL OF IMMUNOLOGY, 2000, 165 (06) : 3043 - 3050
  • [10] Control of regulatory T cell development by the transcription factor Foxp3
    Hori, S
    Nomura, T
    Sakaguchi, S
    [J]. SCIENCE, 2003, 299 (5609) : 1057 - 1061