Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 105, Issue 25, Pages 8691-8696Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0803732105
Keywords
homeostasis; thymus; lymphopenia; CD4 depletion; T cell life span
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Funding
- Medical Research Council [MC_U117565359] Funding Source: Medline
- Medical Research Council [MC_U117565359] Funding Source: researchfish
- MRC [MC_U117565359] Funding Source: UKRI
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A model of chemical thymectomy by inducible Rag ablation was used to study peripheral T cell homeostasis. Induction of Rag ablation was efficient and complete, leading to cessation of thymic T cell production within 3-4 weeks. The decay of peripheral T cells became apparent with a delay of an additional 2-3 weeks and was entirely accounted for by loss of naive T cells, whereas numbers of memory phenotype and regulatory T cells were not decreased. Naive CD4 T cells decayed with an average half-life of 50 days, whereas naive CD8 T cells exhibited a considerably longer half-life. The rapid decay of naive CD4 T cells was not caused by intrinsic survival differences compared with naive CD8 T cells, but was caused by changes in the lymphopenic environment resulting in higher microbial load and consequential activation. This finding suggests that in lymphopenic conditions involving compromised thymic function replenishment and survival of a naive CD4 T cell repertoire may be severely curtailed because of chronic activation. Such a scenario might play a role in the aging immune system and chronic viral infection, such as HIV infection, and contribute to loss of CD4 T cells and impaired immune function. As our data show, continued replenishment with cells from the thymus seems to be required to maintain efficient gut mucosal defense.
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