IL-4 responsive CD4+ T cells specific for myelin basic protein:: IL-2 confers a prolonged postactivation refractory phase

被引:16
作者
Mannie, MD [1 ]
Fraser, DJ [1 ]
Mcconnell, TJ [1 ]
机构
[1] E Carolina Univ, Sch Med, Dept Microbiol & Immunol, Greenville, NC 27858 USA
关键词
antigen presentation; experimental autoimmune encephalomyelitis; major histocompatibility complex; multiple sclerosis; T cells; T cell receptors;
D O I
10.1046/j.1440-1711.2003.01131.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
This study compared myelin basic protein-specific T cells from Lewis rats that were derived in the presence of either rat IL-4 or IL-2. Interleukin-4 was a maintenance factor that enabled derivation of long-term T cell lines. When activated, IL-4 dependent lines were lacking in IL-2 production capacity but maintained high levels of responsiveness to IL-2 and recognized IL-2 as a dominant growth factor. Activated IL-4 dependent T cells rapidly reverted to a quiescent phenotype in the presence of IL-4 and rapidly regained myelin basic protein reactivity. In contrast, activated IL-2 dependent T cells that were propagated in IL-2 had a more persistent blastogenic phenotype and a prolonged refractory phase. Interleukin-4 dependent lines that were propagated in IL-2 up-regulated the capacity to produce IL-2 and also acquired prolonged postactivation refractoriness. Thus, IL-2 was a dominant growth factor that conferred prolonged activation-dependent non-responsiveness. The coupling of dominant growth factor activity with prolonged postactivation refractoriness may be associated with the requisite role of IL-2 in homeostatic self-tolerance.
引用
收藏
页码:8 / 19
页数:12
相关论文
共 60 条
[1]   Defective IL-2-mediated IL-2 receptor α chain expression in Stat3-deficient T lymphocytes [J].
Akaishi, H ;
Takeda, K ;
Kaisho, T ;
Shineha, R ;
Satomi, S ;
Takeda, J ;
Akira, S .
INTERNATIONAL IMMUNOLOGY, 1998, 10 (11) :1747-1751
[2]   Induction of T cell unresponsiveness by anti-CD3 antibodies occurs independently of co-stimulatory functions [J].
Andris, F ;
VanMechelen, M ;
DeMattia, F ;
Baus, E ;
Urbain, J ;
Leo, O .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1996, 26 (05) :1187-1195
[3]  
Bettelli E, 1998, J IMMUNOL, V161, P3299
[4]   GROWTH-FACTORS CAN ENHANCE LYMPHOCYTE SURVIVAL WITHOUT COMMITTING THE CELL TO UNDERGO CELL-DIVISION [J].
BOISE, LH ;
MINN, AJ ;
JUNE, CH ;
LINDSTEN, T ;
THOMPSON, CB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (12) :5491-5495
[5]   Regulation of interleukin (IL)-12 receptor β2 subunit expression by endogenous IL-12:: A critical step in the differentiation of pathogenic autoreactive T cells [J].
Chang, JT ;
Shevach, EM ;
Segal, BM .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (06) :969-978
[6]   Role of costimulation in the induction of the IL-12/PL-12 receptor pathway and the development of autoimmunity [J].
Chang, JT ;
Segal, BM ;
Shevach, EM .
JOURNAL OF IMMUNOLOGY, 2000, 164 (01) :100-106
[7]  
Constantinescu CS, 1998, J IMMUNOL, V161, P5097
[8]   Central nervous system expression of IL-10 inhibits autoimmune encephalomyelitis [J].
Cua, DJ ;
Hutchins, B ;
LaFace, DM ;
Stohlman, SA ;
Coffman, RL .
JOURNAL OF IMMUNOLOGY, 2001, 166 (01) :602-608
[9]  
De Mattia F, 1999, J IMMUNOL, V163, P5929
[10]  
Deeths MJ, 1999, J IMMUNOL, V163, P102