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From naive to effector--alterations with aging

P J Linton1, L Haynes, L Tsui

  • 1Sidney Kimmel Cancer Center, San Diego, California, USA.

Immunological Reviews
|February 26, 1998
PubMed
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T-cell aging involves antigen-dependent and independent factors. Diminished interleukin-2 (IL-2) production contributes to age-related CD4 T-cell dysfunction, but IL-2 can restore function.

Area of Science:

  • Immunology
  • Aging Research
  • T-cell Biology

Background:

  • T-cell populations undergo significant changes with age.
  • Aging is associated with altered immune responses and increased susceptibility to infections.
  • The role of antigen exposure in T-cell aging remains incompletely understood.

Purpose of the Study:

  • To investigate the role of antigen in age-related T-cell alterations.
  • To characterize functional deficits in aged naive CD4 T cells.
  • To determine the contribution of interleukin-2 (IL-2) to T-cell aging.

Main Methods:

  • Utilized T-cell receptor transgenic mouse models.
  • Compared immune responses of aged and young mice.
  • Performed in vitro analysis of naive CD4 T-cell proliferation and cytokine production.

Related Experiment Videos

  • Assessed effector cell generation and phenotype.
  • Investigated the effects of IL-2 supplementation and IL-2/IL-2R alpha knockout models.

    • Main Results:

    • Aging-associated CD4 T-cell memory phenotype shift was absent in antigen-deprived transgenic mice, indicating antigen dependence.
    • Aged naive CD4 T cells showed reduced IL-2/IL-3 production, altered P-glycoprotein levels, and impaired proliferation without exogenous cytokines.
    • Aged naive T cells generated fewer and less functional effector cells with lower IL-2 receptor alpha (IL-2R alpha) expression.
    • IL-2 addition rescued aged naive T-cell proliferation and effector generation, producing cells similar to young T cells.
    • Phenotypic and functional changes mirrored those in IL-2 and IL-2R alpha knockout mice.

    Conclusions:

    • Antigenic stimulation plays a crucial role in the age-related shift of CD4 T-cell populations.
    • Reduced IL-2 production is a significant antigen-independent defect contributing to CD4 T-cell aging.
    • Restoring IL-2 levels can ameliorate age-related T-cell functional decline.