4.6 Article

Age-related CD8+ T cell clonal expansions expiress elevated levels of CD122 and CD127 and display defects in perceiving homeostatic signals

Journal

JOURNAL OF IMMUNOLOGY
Volume 177, Issue 5, Pages 2784-2792

Publisher

AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.177.5.2784

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Funding

  1. NCRR NIH HHS [RR0163] Funding Source: Medline
  2. NIAID NIH HHS [5T32 AI007472-10] Funding Source: Medline
  3. NIA NIH HHS [AG20719, R01 AG020719] Funding Source: Medline

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Aging is accompanied by numerous changes in T cell biology. Among the most dramatic changes at the population level are the appearance and persistence of CD8(+) T cell clonal expansions (TCE), whose frequency increases steadily with age, and whose biology is incompletely understood. In this study, we examined trafficking, phenotypic makeup, and homeostatic responsiveness of TCE, which arise spontaneously in specific pathogen-free mice. We show that these cells make up a specialized subset of central memory T cells with distinguishable phenotypic characteristics, most notably the higher expression of CD122 and CD127, molecules that make up IL-15R and IL-7R, respectively, than other memory T cells. We confirm that these cells proliferate at a continuous pace upon adoptive transfer into the eulymphoid recipient, unlike their non-TCE memory-phenotype counterparts, which remain undivided and die. However, upon transfer into lymphopenic recipients, TCE fail to rapidly expand, but rather resume their slow, continuous proliferation. The above results are discussed in light of possible mechanisms that afford selective survival advantage to TCE over other T cells in an aged T lymphocyte pool.

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