Programmed death-1 (PD-1) defines a transient and dysfunctional oligoclonal T cell population in acute homeostatic proliferation

Sue Jane Lin, Craig D. Peacock, Kapil Bahl, Raymond M. Welsh

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


The host responds to lymphopenic environments by acute homeostatic proliferation, which is a cytokine- and endogenous peptide-driven expansion of lymphocytes that restores the numbers and diversity of T cells. It is unknown how these homeostatically proliferating (HP) cells are ultimately controlled. Using a system where lymphocytic choriomeningitis virus-immune C57BL/6 splenocytes were transferred into lymphopenic T cell-deficient hosts and allowed to reconstitute the environment, we defined the following three populations of T cells: slowly dividing Ly6C+ cells, which contained bona fide virus-specific memory cells, and more rapidly dividing Ly6C- cells segregating into programmed death (PD)-1+ and PD-1? fractions. The PD-1+ HP cell population, which peaked in frequency at day 21, was dysfunctional in that it failed to produce interferon γ or tumor necrosis factor α on T cell receptor (TCR) stimulation, had down-regulated expression of interleukin (IL)-7Rα, IL-15Rβ, and Bcl-2, and reacted with Annexin V, which is indicative of a preapoptotic state. The PD-1+ HP cells, in contrast to other HP cell fractions, displayed highly skewed TCR repertoires, which is indicative of oligoclonal expansion; these skewed repertoires and the PD-1+ population disappeared by day 70 from the host, presumably because of apoptosis. These results suggest that PD-1 may play a negative regulatory role to control rapidly proliferating and potentially pathogenic autoreactive CD8+ T cells during homeostatic reconstitution of lymphopenic environments. JEM

Original languageEnglish (US)
Pages (from-to)2321-2333
Number of pages13
JournalJournal of Experimental Medicine
Issue number10
StatePublished - Oct 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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