Age-related impairment of T cell-induced skeletal muscle precursor cell function

作者:Dumke Breanna R; Lees Simon J*
来源:American Journal of Physiology - Cell Physiology, 2011, 300(6): C1226-C1233.
DOI:10.1152/ajpcell.00354.2010

摘要

Dumke BR, Lees SJ. Age-related impairment of T cell-induced skeletal muscle precursor cell function. Am J Physiol Cell Physiol 300: C1226-C1233, 2011. First published February 16, 2011; doi: 10.1152/ajpcell.00354.2010.-Sarcopenia is the age-associated loss of skeletal muscle mass and strength. Recent evidence suggests that an age-associated loss of muscle precursor cell (MPC) functionality contributes to sarcopenia. The objectives of the present study were to examine the influence of activated T cells on MPCs and determine whether an age-related defect in this signaling occurs. MPCs were collected from the gastrocnemius and plantaris of 3-mo-old (young) and 32-mo-old (old) animals. Splenic T cells were harvested using anti-CD3 Dynabead isolation. T cells were activated for 48 h with costimulation of 100 IU/ml interleukin-2 (IL-2) and 5 mu g/ml of anti-CD28. Costimulation increased 5-bromo-2'-deoxyuridine incorporation of T cells from 13.4 +/- 4.6% in control to 64.8 +/- 6.0% in costimulated cells. Additionally, T cell cytokines increased proliferation on MPCs isolated from young muscle by 24.0 +/- 5.7%, whereas there was no effect on MPCs isolated from aged muscle. T cell cytokines were also found to be a chemoattractant. T cells were able to promote migration of MPCs isolated from young muscle; however, MPCs isolated from aged muscle did not respond to the T cell-released chemokines. Conversely, whereas T cell-released cytokines did not affect myogenesis of MPCs isolated from young animals, there was a decrease in MPCs isolated from old animals. These data suggest that T cells may play a critical role in mediating MPC function. Furthermore, aging may alter T cell-induced MPC function. These findings have implications for developing strategies aimed at increasing MPC migration and proliferation leading to an improved regenerative capacity of aged skeletal muscle.

  • 出版日期2011-6