Regulating functional cell fates in CD8 T cells

被引:47
作者
Shrikant, Protul A. [1 ]
Rao, Rajesh [1 ]
Li, Qingsheng [1 ]
Kesterson, Joshua [1 ]
Eppolito, Cheryl [1 ]
Mischo, Axel [1 ]
Singhal, Pankaj [1 ]
机构
[1] Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA
关键词
CD8(+) T cell; Cytokines; Transcriptional regulators; Effector and memory cell fate; Adoptive cell transfer and tumor immunity; IL-7; RECEPTOR-ALPHA; IN-VIVO; CLONAL EXPANSION; CUTTING EDGE; TRANSCRIPTION FACTOR; LINEAGE COMMITMENT; VIRAL-INFECTION; VIRUS-INFECTION; METASTATIC MELANOMA; CO-STIMULATION;
D O I
10.1007/s12026-009-8130-9
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The attributes of specificity and memory enable CD8(+) T cells to provide long-lasting protection against a variety of challenges. Although, the importance of CD8(+) T cells for protection against intracellular infections and transformation is well-established, the functional type; effector phenotypes (Tc1, Tc2, Tc17 and/or Tcreg) and/or memory (effector or central), of CD8(+) T cells most desirable for tumor immunity is not established. To determine the tumor efficacy of various effector types and/or memory CD8 T cells, it is imperative to better understand intrinsic and extrinsic factors that regulate CD8(+) T cell differentiation and use this information to generate and test distinct functional cell types in tumor models. The focus of our laboratory investigations is to identify the extrinsic factors such as antigen strength, co-stimulatory molecules, cytokines, and small molecule modifiers that regulate intrinsic programs for various effector and/or memory cell fate in antigen specific CD8 T cells. The use of this information to generate immunity in murine tumor models has facilitated development of new adoptive cell transfer (ACT) as well as immunization strategies for cancer treatment.
引用
收藏
页码:12 / 22
页数:11
相关论文
共 88 条
[1]   mTOR regulates memory CD8 T-cell differentiation [J].
Araki, Koichi ;
Turner, Alexandra P. ;
Shaffer, Virginia Oliva ;
Gangappa, Shivaprakash ;
Keller, Susanne A. ;
Bachmann, Martin F. ;
Larsen, Christian P. ;
Ahmed, Rafi .
NATURE, 2009, 460 (7251) :108-U124
[2]   CD8+ T cell contraction is controlled by early inflammation [J].
Badovinac, VP ;
Porter, BB ;
Harty, JT .
NATURE IMMUNOLOGY, 2004, 5 (08) :809-817
[3]   TH-17 cells in the circle of immunity and autoimmunity [J].
Bettelli, Estelle ;
Oukka, Mohamed ;
Kuchroo, Vijay K. .
NATURE IMMUNOLOGY, 2007, 8 (04) :345-350
[4]   The CD8 response on autopilot [J].
Bevan, MJ ;
Fink, PJ .
NATURE IMMUNOLOGY, 2001, 2 (05) :381-382
[5]   Memory CD8+ T cells require CD28 costimulation [J].
Borowski, Annie B. ;
Boesteanu, Alina C. ;
Mueller, Yvonne M. ;
Carafides, Caterina ;
Topham, David J. ;
Altman, John D. ;
Jennings, Stephen R. ;
Katsikis, Peter D. .
JOURNAL OF IMMUNOLOGY, 2007, 179 (10) :6494-6503
[6]   A role for CD40 expression on CD8+ T cells in the generation of CD8+ T cell memory [J].
Bourgeois, C ;
Rocha, B ;
Tanchot, C .
SCIENCE, 2002, 297 (5589) :2060-2063
[7]   IL-7: maintaining T-cell memory and achieving homeostasis [J].
Bradley, LM ;
Haynes, L ;
Swain, SL .
TRENDS IN IMMUNOLOGY, 2005, 26 (03) :172-176
[8]   The density of peptides displayed by dendritic cells affects immune responses to human tyrosinase and gp100 in HLA-A2 transgenic mice [J].
Bullock, TNJ ;
Colella, TA ;
Engelhard, VH .
JOURNAL OF IMMUNOLOGY, 2000, 164 (05) :2354-2361
[9]   Massive expansion of antigen-specific CD8+ T cells during an acute virus infection [J].
Butz, EA ;
Bevan, MJ .
IMMUNITY, 1998, 8 (02) :167-175
[10]   Non-redundant role for IL-7R signaling for the survival of CD8+ memory T cells [J].
Carrio, Roberto ;
Rolle, Cleo E. ;
Malek, Thomas R. .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2007, 37 (11) :3078-3088