Alterations with age in peripheral blood lymphocyte subpopulations and cytokine synthesis in beagles

Abstract

Megumi Fujiwara,1,2 Tomohiro Yonezawa,3 Toshiro Arai,1 Ichiro Yamamoto,1 Hiromichi Ohtsuka21Laboratory of Veterinary Biochemistry, Nippon Veterinary and Life Science University, Tokyo, Japan; 2Laboratory of Large Animal Internal Medicine, 3Laboratory of Veterinary Physiology, Kitasato University, Towada, JapanPurpose: The immune system is considered to be affected by aging, which is linked to various immune pathogeneses. The purpose of this study was to determine age-associated changes in immune function of healthy dogs (beagles), specifically those of naive and memory T lymphocytes, based on cytokine synthesis.Patients and methods: Blood samples were obtained from 44 healthy beagles that were divided into three age-groups: young (<4 years), middle-aged (4–8 years), and older dogs (>8 years). Subpopulations of T lymphocytes were determined by flow cytometry. Transcriptional (mRNA) levels of cytokines were determined for primary-cultured leukocytes using quantitative real-time polymerase chain reaction.Results: There were negative correlations between dogs’ages and the number of peripheral blood mononuclear cells, T cells, and B cells. In particular, the number of naive CD4+ CD45RA+ T cells and CD8+ CD45RA+ T cells significantly decreased with age. The mRNA levels for interleukin (IL)-2, IL-2Rα, and interferon-gamma were significantly higher in young or middle-aged dogs (P < 0.05), whereas IL-4 mRNA expression was not significantly different over the different age-groups. IL-2Rγ mRNA expression tended to decrease with age.Conclusion: Decreases of naive CD4+ and naive CD8+ T cells may be related to age-related immunosenescence in dogs. With regard to cytokine production, leukocyte IL-4 and IL-10 mRNA levels did not change with age, whereas IL-2, IL-2Rα, and IL-2Rγ mRNA levels decreased with age. These altered cytokine mRNA expression patterns may contribute to decreased naive T-cell function(s) with aging.Keywords: aging, leukocyte subpopulation, cytokine, dog, naive T cell, IL-2R