Open AccessCharacterization of age‐associated exhausted CD 8 + T cells defined by increased expression of Tim‐3 and PD ‐1
Author(s) -
Lee KyooA,
Shin KwangSoo,
Kim GaYoung,
Song You Chan,
Bae EunAh,
Kim IlKyu,
Koh ChoongHyun,
Kang ChangYuil
Publication year - 2016
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12435
Subject(s) - biology , immune system , t cell , population , microbiology and biotechnology , antigen , immunology , receptor , t cell receptor , homeostasis , medicine , biochemistry , environmental health
Summary Aging is accompanied by altered T‐cell responses that result in susceptibility to various diseases. Previous findings on the increased expression of inhibitory receptors, such as programmed cell death protein 1 ( PD ‐1), in the T cells of aged mice emphasize the importance of investigations into the relationship between T‐cell exhaustion and aging‐associated immune dysfunction. In this study, we demonstrate that T‐cell immunoglobulin mucin domain‐3 (Tim‐3), another exhaustion marker, is up‐regulated on aged T cells, especially CD 8 + T cells. Tim‐3‐expressing cells also produced PD ‐1, but Tim‐3 + PD ‐1 + CD 8 + T cells had a distinct phenotype that included the expression of CD 44 and CD 62L, from Tim‐3 − PD ‐1 + cells. Tim‐3 + PD ‐1 + CD 8 + T cells showed more evident properties associated with exhaustion than Tim‐3 − PD ‐1 + CD 8 + T cells: an exhaustion‐related marker expression profile, proliferative defects following homeostatic or TCR stimulation, and altered production of cytokines. Interestingly, these cells produced a high level of IL ‐10 and induced normal CD 8 + T cells to produce IL ‐10, which might contribute to immune dysregulation in aged mice. The generation of Tim‐3‐expressing CD 8 + T cells in aged mice seems to be mediated by encounters with antigens but not by specific infection, based on their high expression of CD 49d and their unbiased TCR Vβ usage. In conclusion, we found that a CD 8 + T‐cell population with age‐associated exhaustion was distinguishable by its expression of Tim‐3. These results provide clues for understanding the alterations that occur in T‐cell populations with age and for improving dysfunctions related to the aging of the immune system.