Abnormal regulation of T lymphocytes from aged rats contributes to immunosenescence
Franklin, Richard Arnold
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Permalink
https://hdl.handle.net/2142/20216
Description
Title
Abnormal regulation of T lymphocytes from aged rats contributes to immunosenescence
Author(s)
Franklin, Richard Arnold
Issue Date
1989
Doctoral Committee Chair(s)
Kelley, Keith W.
Department of Study
Animal Sciences
Discipline
Animal Sciences
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, General
Language
eng
Abstract
Regulation of T lymphocyte proliferation from aged rats was explored by activating lymphocytes to proliferate with the T cell lectin Con A, the calcium ionophores A23187 and ionomycin and the protein kinase C activator, PMA. Similar to human T lymphocytes, but unlike mouse lymphocytes, rat splenocytes and T lymphocytes proliferate in response to calcium ionophores in the absence of detectable IL 2 or IL 4. Proliferation in response to ionomycin and A23187 increases as early as 6 months of age and continues to rise until 24 months of age, and this increase precedes the decline in proliferative responses of splenocytes to Con A. The enhanced response of splenocytes and T lymphocytes to ionomycin is a newly-defined, very sensitive biomarker of aging.
Proliferative responses of Con A-activated splenocytes and nylon wool-enriched T lymphocytes from young and old rats were then compared. It was discovered that the well-described decline in Con A-induced splenocyte proliferation that occurs with age precedes any age-associated proliferative defect in the Con A-induced activation of enriched populations of T lymphocytes. PMA, in combination with ionomycin, partially reversed the decline in proliferation of splenocytes from aged rats, suggesting that defects occur in transmembrane signaling during the aging process. Three substances that are secreted by cells which are abundant in splenocyte culture compared to enriched populations of T lymphocytes are PG-E$\sb2$, TGF-b2 and H$\sb2$O$\sb2$. All three of these compounds suppress Con A-induced proliferative responses of splenocytes from aged rats to a significantly greater degree than in cells from young rats. These data indicate that the age-associated decline in Con A-induced proliferation of splenocytes is triggered by products liberated from nylon wool-adherent cells. The possibility that a defective glutathione-dependent detoxification system is responsible for the reduction in Con A-induced proliferation of splenocytes from old rats was explored. Reduced glutathione (GSH), as well as substances which increase the GSH content of lymphocytes (cysteine and 2-ME), augment Con A-induced proliferative responses of splenocytes from old rats (8 to 10 fold) to a significantly greater degree than in young rats (2 fold). However, this enhancement is not caused by increasing expression of transferrin receptors, which are required for mitogen-induced proliferation of T lymphocytes, to a greater degree on T cells from old rats compared to young animals. These data are consistent with the idea that T lymphocytes become increasingly susceptible to inhibitory products released by nylon wool-adherent cells during the aging process.
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