In:
Aging Cell, Wiley, Vol. 14, No. 5 ( 2015-10), p. 744-753
Abstract:
Insight into the maintenance of naive T cells is essential to understand defective immune responses in the context of aging and other immune compromised states. In humans, naive CD 4+ T cells, in contrast to CD 8+ T cells, are remarkably well retained with aging. Here, we show that low‐affinity TCR engagement is the main driving force behind the emergence and accumulation of naive‐like CD 4+ T cells with enhanced sensitivity to IL ‐2 in aged humans. In vitro, we show that these CD 45 RA + CD 25 dim CD 4 + T cells can develop from conventional naive CD 25 − CD 4+ T cells upon CD 3 cross‐linking alone, in the absence of costimulation, rather than via stimulation by the homeostatic cytokines IL ‐2, IL ‐7, or IL ‐15. In vivo , TCR engagement likely occurs in secondary lymphoid organs as these cells were detected in lymph nodes and spleen where they showed signs of recent activation. CD 45 RA + CD 25 dim CD 4+ T cells expressed a broad TCRV β repertoire and could readily differentiate into functional T helper cells. Strikingly, no expansion of CD 45 RA + CD 25 dim CD 8+ T cells was detected with aging, thereby implying that maintenance of naive CD 4+ T cells is uniquely regulated. Our data provide novel insight into the homeostasis of naive T cells and may guide the development of therapies to preserve or restore immunity in the elderly.
Type of Medium:
Online Resource
ISSN:
1474-9718
,
1474-9726
DOI:
10.1111/acel.2015.14.issue-5
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2099130-7
SSG:
12
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