TY - JOUR
T1 - Role of cell-intrinsic and environmental age-related changes in altered maintenance of murine T cells in lymphoid organs
AU - Davies, John S.
AU - Thompson, Heather L.
AU - Pulko, Vesna
AU - Torres, Jose Padilla
AU - Nikolich-Žugich, Janko
N1 - Funding Information:
Supported by the NIAID (National Institute on Aging, National Institutes of Health) contract ADBS (N01-AI000017) and the Bowman Endowed Professorship in Medical Sciences (to J.N-Ž).
Publisher Copyright:
© The Author(s) 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights
PY - 2018/7/9
Y1 - 2018/7/9
N2 - Age-related changes in primary lymphoid organs are well described. Less is known about age-related changes affecting peripheral lymphoid organs, although defects in old peripheral lymph nodes (pLNs) were recently described in both steady state and during viral infection. To address whether such pLN defects were intrinsic to old T cells or extrinsic (due to aging microenvironment), we employed heterochronic parabiosis. We found no age-related intrinsic or extrinsic barriers to T cell circulation and seeding of pLN, spleen, and bone marrow. However, heterochronic parabiosis failed to improve cellularity of old pLN, suggesting an environment-based limit on pLN cellularity. Furthermore, upon parabiosis, pLN of the adult partner exhibited reduced, old-like stromal and T cell cellularity, which was restored following separation of parabionts. Decay measurement of adult and old T cell subsets following separation of heterochronic parabionts delineated both T cell-intrinsic and environmental changes in T cell maintenance. Moreover, parabiotic separation revealed differences between CD4 and CD8 T cell subset maintenance with aging, the basis of which will require further investigation. Reasons for this asymmetric and subset-specific pattern of differential maintenance are discussed in light of possible age-related changes in lymph nodes as the key sites for peripheral T cell maintenance.
AB - Age-related changes in primary lymphoid organs are well described. Less is known about age-related changes affecting peripheral lymphoid organs, although defects in old peripheral lymph nodes (pLNs) were recently described in both steady state and during viral infection. To address whether such pLN defects were intrinsic to old T cells or extrinsic (due to aging microenvironment), we employed heterochronic parabiosis. We found no age-related intrinsic or extrinsic barriers to T cell circulation and seeding of pLN, spleen, and bone marrow. However, heterochronic parabiosis failed to improve cellularity of old pLN, suggesting an environment-based limit on pLN cellularity. Furthermore, upon parabiosis, pLN of the adult partner exhibited reduced, old-like stromal and T cell cellularity, which was restored following separation of parabionts. Decay measurement of adult and old T cell subsets following separation of heterochronic parabionts delineated both T cell-intrinsic and environmental changes in T cell maintenance. Moreover, parabiotic separation revealed differences between CD4 and CD8 T cell subset maintenance with aging, the basis of which will require further investigation. Reasons for this asymmetric and subset-specific pattern of differential maintenance are discussed in light of possible age-related changes in lymph nodes as the key sites for peripheral T cell maintenance.
KW - Homeostasis-Lymph nodes-T cells-Parabiosis-Aging
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U2 - 10.1093/gerona/glx102
DO - 10.1093/gerona/glx102
M3 - Article
C2 - 28582491
AN - SCOPUS:85021201208
VL - 73
SP - 1018
EP - 1026
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
SN - 1079-5006
IS - 8
ER -