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ARTICLE |
CORRESPONDENCE Raymond M. Welsh: Raymond.Welsh{at}umassmed.edu
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
or tumor necrosis factor 
on T cell receptor (TCR) stimulation, had down-regulated expression of interleukin (IL)-7R, IL-15Rß, 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.
C.D. Peacock's present address is The Sydney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21231.
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