Advanced age in horses affects divisional history of T cells and inflammatory cytokine production.
Abstract: A number of model systems have been employed to investigate age-associated changes in immune function. The purpose of the current study was to characterize senescent T cells and to investigate the inflamm-aging phenomenon both in vitro and in vivo using the old horse as a model. We examined whether decreased T cell proliferation induced by Con A is caused by increased apoptosis. We also utilized intracellular CFSE to analyze changes within each round of cell proliferation, in particular cytokine production. Intracellular staining with flow cytometry, RT-PCR, and ELISA were used to measure pro-inflammatory cytokines both in vitro and in vivo. While lymphocytes from old horses exhibit decreased proliferation, this is not the result of increased apoptosis. Instead, a larger percentage of the T cells remain in the parent generation and produce significant amounts of IFNgamma. Likewise, old horses have increased frequency of CD8-IFNgamma+ T cells and TNFalpha producing cells. We also show that old horses have elevated levels of IL-1beta, IL-15, IL-18 and TNFalpha gene expression in peripheral blood and significant levels of TNFalpha protein in serum, all characteristics of inflamm-aging.
Publication Date: 2008-09-24 PubMed ID: 18926847DOI: 10.1016/j.mad.2008.09.004Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research examines how advanced age in horses affects T cell division and inflamatory cytokine production. The study investigates the production of pro-inflammatory cytokines, decreased T cell proliferation, and the presence of inflamm-aging in older horses.
Understanding Immune Function and Aging in Horses
- The study aims to understand the changes in immune function due to aging, focusing on aging T cells and inflammation, both in vitro and in vivo. It uses old horses as the model to conduct this research.
- Using various tests like flow cytometry, RT-PCR, and ELISA, the scientists analyze the production of pro-inflammatory cytokines in the test samples. These are proteins that our immune system produces when there’s inflammation or when our cells are damaged.
Investigation into Decreased T Cell Proliferation
- The researchers checked whether diminished T cell proliferation initiated by Con A is due to increased apoptosis or programmed cell death. Pretty much like how our skin cells shed and regrow, T cells, a type of white blood cell, also undergo a cycle where they grow and die.
- However, they found that lymphocytes, another type of white blood cell, from old horses, showed decreased proliferation but not due to increased apoptosis. Instead, many of these cells remained in the ‘parent generation’, referring to their origin before dividing or proliferating.
- These remaining T cells, interestingly, produced significant amounts of IFNgamma, a type of cytokine that plays a crucial role in immunity against viral and microbial agents. This could potentially shed light on how immune response changes with age.
Demonstrating Inflamm-Aging
- The research showed that old horses had a higher frequency of CD8-IFNgamma+ T cells and TNFalpha or Tumor Necrosis Factor alpha producing cells. TNFalpha is a cell signaling protein (cytokine) involved in systemic inflammation, suggesting an increased inflammatory response in aged horses.
- The aged horses also had higher levels of gene expression for IL-1beta, IL-15, IL-18, and TNFalpha in peripheral blood, and significant levels of TNFalpha protein in serum, a characteristic of ‘inflamm-aging’. Inflamm-aging is a condition characterized by elevated inflammation with advanced age, a phenomenon observed across several species and is also associated with many age-related diseases.
Significance of the Findings
- The findings from this study provide valuable insights into understanding how immune function changes with age.
- It reveals the key role that T cells play in this process and how their proliferation and various cytokine production alters in the aging process.
- Such knowledge can potentially help develop targeted therapies or interventions that could mitigate these age-associated changes in immune function, possibly leading to increased healthspan in horses and potentially other mammalian species.
Cite This Article
APA
Adams AA, Breathnach CC, Katepalli MP, Kohler K, Horohov DW.
(2008).
Advanced age in horses affects divisional history of T cells and inflammatory cytokine production.
Mech Ageing Dev, 129(11), 656-664.
https://doi.org/10.1016/j.mad.2008.09.004 Publication
Researcher Affiliations
- Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546-0099, United States.
MeSH Terms
- Age Factors
- Aging / immunology
- Animals
- Apoptosis / drug effects
- Cell Proliferation / drug effects
- Cells, Cultured
- Cellular Senescence
- Concanavalin A / pharmacology
- Cytokines / genetics
- Cytokines / metabolism
- Horses
- Inflammation Mediators / metabolism
- Interferon-gamma / blood
- Interleukins / blood
- Mitogens / pharmacology
- Models, Animal
- RNA, Messenger / blood
- T-Lymphocytes / drug effects
- T-Lymphocytes / immunology
- Tumor Necrosis Factor-alpha / blood
Citations
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