Effect of aging on T lymphocyte activation

被引：96

作者：

Miller, RA ^{[1
]}

机构：

[1] Univ Michigan, Sch Med, Dept Pathol, Inst Gerontol, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Sch Med, Geriatr Ctr, Inst Gerontol, Ann Arbor, MI 48109 USA

[3] Ann Arbor VA Med Ctr, Ann Arbor, MI 48109 USA

来源：

VACCINE | 2000年 / 18卷 / 16期

关键词：

protein kinase C; c-Jun N-terminal kinase; T-cell activation; signal transduction; immune senescence;

D O I：

10.1016/S0264-410X(99)00502-2

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Studies of the early stages of T-cell activation reveal that T cells from aged mice show multiple abnormalities within the first few minutes after stimulation, including decline in the activation of the Raf-1/MEK/ERK kinases and in JNK protein kinase. Zap-70 kinase associated with the CD3 zeta chain shows a 2-fold increase with age in resting CD4 T cells, despite a three-fold decline with age in the levels of tyrosine phosphorylation of CD3 zeta; nonetheless, there is no effect of aging on Zap-70 kinase function in activated T cells as measured by in vitro kinase methods. Age-related impairment of the translocation of PKC theta from cytoplasm to the site of T-cell interaction with antigen-presenting cells may underlie downstream defects in the activation cascade. (C) 2000 Elsevier Science Ltd. All rights reserved.

引用

页码：1654 / 1660

页数：7

共 18 条

[1] Differential signaling by lymphocyte antigen receptors [J].

AlberolaIla, J ;

Takaki, S ;

Kerner, JD ;

Perlmutter, RM .

ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 :125-154

[2] ACTIVATION-INDUCED UBIQUITINATION OF THE T-CELL ANTIGEN RECEPTOR [J].

CENCIARELLI, C ;

HOU, D ;

HSU, KC ;

RELLAHAN, BL ;

WIEST, DL ;

SMITH, HT ;

FRIED, VA ;

WEISSMAN, AM .

SCIENCE, 1992, 257 (5071) :795-797

[3] THE ROLE OF PROTEIN-TYROSINE KINASES AND PROTEIN-TYROSINE PHOSPHATASES IN T-CELL ANTIGEN RECEPTOR SIGNAL-TRANSDUCTION [J].

CHAN, AC ;

DESAI, DM ;

WEISS, A .

ANNUAL REVIEW OF IMMUNOLOGY, 1994, 12 :555-592

[4] Increased Zap-70 association with CD3ζ in CD4 T cells from old mice [J].

Garcia, GG ;

Miller, RA .

CELLULAR IMMUNOLOGY, 1998, 190 (02) :91-100

[5] Differential tyrosine phosphorylation of zeta chain dimers in mouse CD4 T lymphocytes: Effect of age [J].

Garcia, GG ;

Miller, RA .

CELLULAR IMMUNOLOGY, 1997, 175 (01) :51-57

[6] RAPID TYROSINE PHOSPHORYLATION OF GRB2 AND SHC IN T-CELLS EXPOSED TO ANTI-CD3, ANTI-CD4, AND ANTI-CD45 STIMULI - DIFFERENTIAL-EFFECTS OF AGING [J].

GHOSH, J ;

MILLER, RA .

MECHANISMS OF AGEING AND DEVELOPMENT, 1995, 80 (03) :171-187

[7] Diminished activation of the MAP kinase pathway in CD3-stimulated T lymphocytes from old mice [J].

Gorgas, G ;

Butch, ER ;

Guan, KL ;

Miller, RA .

MECHANISMS OF AGEING AND DEVELOPMENT, 1997, 94 (1-3) :71-83

[8] Fidelity of T cell activation through multistep T cell receptor ζ phosphorylation [J].

Kersh, EN ;

Shaw, AS ;

Allen, PM .

SCIENCE, 1998, 281 (5376) :572-575

[9] Analysis of Raf-1 activation in response to TCR activation and costimulation in murine T-lymphocytes: Effect of age [J].

Kirk, CJ ;

Miller, RA .

CELLULAR IMMUNOLOGY, 1998, 190 (01) :33-42

[10] Three-dimensional segregation of supramolecular activation clusters in T cells [J].

Monks, CRF ;

Freiberg, BA ;

Kupfer, H ;

Sciaky, N ;

Kupfer, A .

NATURE, 1998, 395 (6697) :82-86

← 1 2 →