Defective CD8 T Cell Responses in Aged Mice Are Due to Quantitative and Qualitative Changes in Virus-Specific Precursors

被引：106

作者：

Decman, Vilma ^{[1
,2
]}

Laidlaw, Brian J. ^{[1
,2
]}

Doering, Travis A. ^{[1
,2
]}

Leng, Jin ^{[3
,4
]}

Ertl, Hildegund C. J. ^{[5
]}

Goldstein, Daniel R. ^{[3
,4
]}

Wherry, E. John ^{[1
,2
]}

机构：

[1] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA

[2] Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA

[3] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA

[4] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06510 USA

[5] Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA

来源：

JOURNAL OF IMMUNOLOGY | 2012年 / 188卷 / 04期

基金：

美国国家卫生研究院;

关键词：

MEMORY-PHENOTYPE CELLS; CLONAL EXPANSIONS; HOMEOSTATIC PROLIFERATION; REPERTOIRE DIVERSITY; INFECTION; IMMUNITY; PD-1; GENERATION; FREQUENCY; VACCINATION;

D O I：

10.4049/jimmunol.1101098

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Aging is associated with suboptimal CD8 T cell responses to viral infections. It is not clear whether these poor responses are due to environmental influences or quantitative and qualitative changes in the pool of responding CD8 T cells. Our studies demonstrated several deleterious age-related changes in the pool of Ag-specific CD8 T cells that respond to infection. The majority of CD8 T cells from uninfected aged mice was CD44(Hi) and had increased expression of inhibitory receptors including PD1, LAG3, 2B4, and CD160. These aged CD44(Hi) CD8 T cells were transcriptionally similar to exhausted CD8 T cells found during chronic infections. In addition, the number of virus-specific precursors in aged mice prior to infection was decreased up to 10-fold, and many of these Ag-specific precursors had high expression of CD44 and PD1. Finally, TCR transgenic studies demonstrated that the CD44(Hi) Ag-specific CD8 T cells from unimmunized aged and young mice were qualitatively inferior compared with CD44(Lo) CD8 T cells from aged or young donors. Thus, a decrease in precursor frequency as well as qualitative changes of CD8 T cells during aging are directly related to impaired immunity. The Journal of Immunology, 2012, 188: 1933-1941.

引用

页码：1933 / 1941

页数：9

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