Immune system dysfunction during aging is well documented fact. Changes in the adaptive immune system are the most marked, especially in the T-cell compartment. In multiple preliminary studies it has been shown that parabiosis between 2 animals of different age can induce age-related changes in adaptive immune response and T-cell subpopulation composition of younger animal. In present study we evaluated the age-related changes in functions of rapidly renewing (macrophages) and slowly renewing cells (CD11c+ DCs) cells in spleens of young and old parabionts. We observed impaired capacity of splenic adherent cells from younger heterochronic parabionts to co-stimulate proliferation of autologous T-cells in vitro up to the level of old animals. Also we observed negative effect of this splenic cell population on intracellular signaling mechanisms that regulate PHA-activated proliferation of T-cells from young animals: statistically significant decrease of NFκB p65 expression and increased expression of IκBα during early activation events. This fact suggests that splenic macrophages may be involved in the induction of age-related changes of the immune system and they can be prospective target for further investigation.
Published in | American Journal of BioScience (Volume 3, Issue 2) |
DOI | 10.11648/j.ajbio.20150302.14 |
Page(s) | 46-54 |
Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
Copyright |
Copyright © The Author(s), 2015. Published by Science Publishing Group |
CD11c+ Dendritic Cells, Macrophages, Heterochronic Parabiosis, Lymphoid Niche, Aging
[1] | A. Larbi, G. Pawelec, S.C. Wong, D. Goldeck, J.J. Tai, T. Fulop. Aging of the immune system as a prognostic factor for human longevity. Physiology 2008; 23: 64–74. |
[2] | A. M. Holland, V. R. M. van den Brink. Rejuvenation of the aging T cell compartment. Curr. Opin. Immunol. 2009; 21: 454–9. |
[3] | S.L. Swain, J. Nikolich-Zugich. Key research opportunities in immune system aging. J. Gerontol. Biol. Sci. Med. Sci. 2009; 64: 183-6. |
[4] | H. Tsukamoto, K. Clise-Dwyer, G. E. Huston, D. K. Duso, A. L. Buck, L. L. Johnson et al. Age-associated increase in lifespan of naıve CD4 T cells contributes to T-cell homeostasis but facilitates development of functional defects. Proc. Natl. Acad. Sci. USA. 2009; 106: 18333–8. |
[5] | G. M. Butenko, I. B. Gubrii. Inhibition of the immune responses of young adult CBA mice due to parabiosis with their old partners. Exp. Geront. 1980; 15: 605-10. |
[6] | Z. Deyl, G. M. Butenko, J. Hausmann, M. Horakova, K. Macek. Increased glycation and pigmentation of collagen in aged and young parabiotic rats and mice. Mech. Aging. Develop. 1990; 55: 39-49. |
[7] | S. A. Villeda, J. Luo, K. I. Mosher, B. Zou, M. Britschgi, G. Bieri et al. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature. 2011; 477: 90-4. |
[8] | I. Pishel, D. Shytikov, T. Orlova, A. Peregudov, I. Artyuhov, G. Butenko. Accelerated aging versus rejuvenation of the immune system in heterochronic parabiosis. Rejuvenation. Res. 2012; 15: 239-48. |
[9] | G. M. Butenko, I. B. Gubriĭ. Mechanism of immune response inhibition during parabiosis of animals of different ages. Biull. Eksp. Biol. Med. 1981; 92: 318-9. |
[10] | N. Cools, P. Ponsaerts, V. F. Van Tendeloo, Z. N. Berneman. Balancing between immunity and tolerance: an interplay between dendritic cells, regulatory T cells, and effector T cells. J. Leukoc. Biol 2007; 82: 1365-74. |
[11] | D. A. Hume. Macrophages as APC and the Dendritic Cell Myth. J. Immunol. 2008; 181: 5829-35. |
[12] | F. K. Swirski, M. Nahrendorf, M. Etzrodt, M. Wildgruber, V. Cortez-Retamozo, P. Panizzi et al. Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science. 2009; 325: 612-16. |
[13] | T. Mosman. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cіtotoхity assay J. Immunol. Metods. 1983; 65: 55-63. |
[14] | K. W. Kaufmann, C.I. Behe, V. M. Golubovskaya, L. L. Byrd, C. D. Albright, K. M. Borchet. Aberrant cell cycle checkpoint function in transformed hepatocytes and WB-F344 hepatic epithelial stem-like cells. Сarcinogenesis 2011; 22: 1257-69. |
[15] | A. Agrawal, S. Agrawal, J. Tay, S. Gupta. Biology of Dendritic Cells in Aging. J. Clin. Immunol.2008; 28: 14–20. |
[16] | A. M. Kruisbeek, E. Shevach, A. M. Thornton. Proliferative Assays for T Cell Function. Current Protocols in Immunology. 2004; 60: III:3.12:3.12.1–3.12.20. |
[17] | J. E. Smith-Garvin, G. A. Koretzky, M. S. Jordan. T cell activation. Annu. Rev. Immunol. 2009; 27: 591-619. |
[18] | F. Geissmann, M. G. Manz, S. Jung, M. H. Sieweke, M. Merad, K. Ley. Development of monocytes, macrophages, and dendritic cells. Science. 2010; 327: 656-61. |
[19] | D. Fooksman, S. Vardhana, G. Vasiliver-Shamis, J. Liese, D. A. Blair, J. Waite. Functional Anatomy of T Cell Activation and Synapse Formation. Annu. Rev. Immunol. 2010; 28: 79–105. |
[20] | O. Boyman, S. Létourneau, C. Krieg, J. Sprent. Homeostatic proliferation and survival of naïve and memory T cells. Eur. J. Immunol. 2009; 39: 2088-94. |
[21] | A. Agrawal, S. Gupta. Impact of Aging on Dendritic Cell Functions in humans. Ageing. Res. Rev. 2011; 10: 336–45. |
[22] | S. Komatsubara, B. Cinader, S. Muramatsu. Polymorphism of age-related changes in stimulatory capacity of murine dendritic cells. Mech. Ageing Dev. 1986; 37: 163–73. |
[23] | N. P. Weng, A. N. Akbar, J. Goronzy. CD28− T cells: their role in the age-associated decline of immune function. Trends Immunol. 2009; 30: 306–12. |
[24] | J. A. Stefater 3rd, S. Ren, R. A. Lang, J. S. Duffeld. Metchnikoff's policemen: macrophages in development, homeostasis and regeneration. Trends Mol. Med. 2011; 17: 743-52. |
[25] | D. M. Mosser, J. P. Edwards. Exploring the full spectrum of macrophage activation. Nat. Rev. Immunol. 2008; 8: 958-69. |
[26] | R. N. Barker, L. P. Erwig, K. S. Hill, A. Devine, W. P. Pearce, A. J. Rees. Antigen presentation by macrophages is enhanced by the uptake of necrotic, but not apoptotic, cells. Clin. Exp. Immunol. 2002; 127: 220–25. |
[27] | R. D. Stout, J. Suttles. Immunosenescence and macrophage functional plasticity: dysregulation of macrophage function by age-associated microenvironmental changes. Immunol. Rev. 2005; 205: 60-71. |
[28] | Y. Sun, H. Li, M. F. Yang, W. Shu, M. J. Sun, Y. Xu. Effects of Aging on Endotoxin Tolerance Induced by Lipopolysaccharides Derived from Porphyromonas gingivalis and Escherichia coli. PLoS ONE 2012; 7:e39224. |
[29] | C. A. Cecílio, E. H. Costa, P. U. Simioni, D. L. Gabriel, W. M. Tamashiro. Aging alters the production of iNOS, arginase and cytokines in murine macrophages. Braz. J. Med. Biol. Res. 2011; 44: 671-81. |
[30] | S. Z. Birjandi, J. A. Ippolito, A. K. Ramadorai, P. L. White. Alterations in marginal zone macrophages and marginal zone B cells in old mice. J. Immunol. 2011; 186: 3441-51. |
[31] | C. Shi, E. G. Pamer. Monocyte recruitment during infection and inflammation. Nat. Rev. Immunol. 2011; 11: 762-74. |
[32] | E. O'Dea, A. Hoffmann. The regulatory logic of the NF-kappaB signaling system. Cold Spring Harb. Perspect. Biol. 2010; 2: a000216. |
[33] | N. S. Lee, L. Barber, A. Kanchwala, C. J. Childs, Y. P. Kataria, M. A. Judson et al. Low levels of NF-κB/p65 mark anergic CD4+ T cells and correlate with disease severity in sarcoidosis. Clin. Vaccine. Immunol. 2011; 18: 223-34. |
[34] | A. Sundstedt, M. Sigvardsson, T. Leanderson, G. Hedlund, T. Kalland, M. Dohlsten. In vivo anergized CD4+ T cells express perturbed AP-1 and NF-kappa B transcription factors. Proc. Natl. Acad. Sci. USA. 1996; 93: 979-84. |
[35] | J. K. Norman, T. Kataokа, J. Tschopp, R. C. Budd. Caspase Activation Is Required for T Cell Proliferation. J. Exp. Med. 1999; 190: 1891–96. |
[36] | M. Coiras, M. R. López-Huertas, E. Mateos, J. Alcami. Caspase-3-mediated cleavage of p65/RelA results in a carboxy-terminal fragment that inhibits IκBα and enhances HIV-1 replication in human T lymphocytes. Retrovirology 2008; 5: 109. |
[37] | S. McComb, R. Mulligan, S. Sad. Caspase-3 Is Transiently Activated without Cell Death during Early Antigen Driven Expansion of CD8+ T Cells In Vivo. PLoS One. 2010; 5: e15328. |
APA Style
Dmytro W. Shytikov, Maryna S. Shkumat, Tetiana M. Yankova, Alex G. Peregudov, Igor V. Artyuhov, et al. (2015). Splenic Niche Cells from Young Heterochronic Parabionts Have Decreased Capability to Amplify T-cell Proliferation in Vitro. American Journal of BioScience, 3(2), 46-54. https://doi.org/10.11648/j.ajbio.20150302.14
ACS Style
Dmytro W. Shytikov; Maryna S. Shkumat; Tetiana M. Yankova; Alex G. Peregudov; Igor V. Artyuhov, et al. Splenic Niche Cells from Young Heterochronic Parabionts Have Decreased Capability to Amplify T-cell Proliferation in Vitro. Am. J. BioScience 2015, 3(2), 46-54. doi: 10.11648/j.ajbio.20150302.14
AMA Style
Dmytro W. Shytikov, Maryna S. Shkumat, Tetiana M. Yankova, Alex G. Peregudov, Igor V. Artyuhov, et al. Splenic Niche Cells from Young Heterochronic Parabionts Have Decreased Capability to Amplify T-cell Proliferation in Vitro. Am J BioScience. 2015;3(2):46-54. doi: 10.11648/j.ajbio.20150302.14
@article{10.11648/j.ajbio.20150302.14, author = {Dmytro W. Shytikov and Maryna S. Shkumat and Tetiana M. Yankova and Alex G. Peregudov and Igor V. Artyuhov and Iryna M. Pishel}, title = {Splenic Niche Cells from Young Heterochronic Parabionts Have Decreased Capability to Amplify T-cell Proliferation in Vitro}, journal = {American Journal of BioScience}, volume = {3}, number = {2}, pages = {46-54}, doi = {10.11648/j.ajbio.20150302.14}, url = {https://doi.org/10.11648/j.ajbio.20150302.14}, eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajbio.20150302.14}, abstract = {Immune system dysfunction during aging is well documented fact. Changes in the adaptive immune system are the most marked, especially in the T-cell compartment. In multiple preliminary studies it has been shown that parabiosis between 2 animals of different age can induce age-related changes in adaptive immune response and T-cell subpopulation composition of younger animal. In present study we evaluated the age-related changes in functions of rapidly renewing (macrophages) and slowly renewing cells (CD11c+ DCs) cells in spleens of young and old parabionts. We observed impaired capacity of splenic adherent cells from younger heterochronic parabionts to co-stimulate proliferation of autologous T-cells in vitro up to the level of old animals. Also we observed negative effect of this splenic cell population on intracellular signaling mechanisms that regulate PHA-activated proliferation of T-cells from young animals: statistically significant decrease of NFκB p65 expression and increased expression of IκBα during early activation events. This fact suggests that splenic macrophages may be involved in the induction of age-related changes of the immune system and they can be prospective target for further investigation.}, year = {2015} }
TY - JOUR T1 - Splenic Niche Cells from Young Heterochronic Parabionts Have Decreased Capability to Amplify T-cell Proliferation in Vitro AU - Dmytro W. Shytikov AU - Maryna S. Shkumat AU - Tetiana M. Yankova AU - Alex G. Peregudov AU - Igor V. Artyuhov AU - Iryna M. Pishel Y1 - 2015/03/02 PY - 2015 N1 - https://doi.org/10.11648/j.ajbio.20150302.14 DO - 10.11648/j.ajbio.20150302.14 T2 - American Journal of BioScience JF - American Journal of BioScience JO - American Journal of BioScience SP - 46 EP - 54 PB - Science Publishing Group SN - 2330-0167 UR - https://doi.org/10.11648/j.ajbio.20150302.14 AB - Immune system dysfunction during aging is well documented fact. Changes in the adaptive immune system are the most marked, especially in the T-cell compartment. In multiple preliminary studies it has been shown that parabiosis between 2 animals of different age can induce age-related changes in adaptive immune response and T-cell subpopulation composition of younger animal. In present study we evaluated the age-related changes in functions of rapidly renewing (macrophages) and slowly renewing cells (CD11c+ DCs) cells in spleens of young and old parabionts. We observed impaired capacity of splenic adherent cells from younger heterochronic parabionts to co-stimulate proliferation of autologous T-cells in vitro up to the level of old animals. Also we observed negative effect of this splenic cell population on intracellular signaling mechanisms that regulate PHA-activated proliferation of T-cells from young animals: statistically significant decrease of NFκB p65 expression and increased expression of IκBα during early activation events. This fact suggests that splenic macrophages may be involved in the induction of age-related changes of the immune system and they can be prospective target for further investigation. VL - 3 IS - 2 ER -