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The Journal of Immunology, 2001, 166: 1524-1530.
Copyright © 2001 by The American Association of Immunologists

IL-7 and Not Stem Cell Factor Reverses Both the Increase in Apoptosis and the Decline in Thymopoiesis Seen in Aged Mice1

Deborah Andrew2 and Richard Aspinall

Department of Immunology, Imperial College of Science and Medicine at Chelsea and Westminster Hospital, London, United Kingdom

Thymic atrophy is an age-associated decline in commitment to the T cell lineage considered to be associated with defective TCR {beta}-chain rearrangement. Both IL-7 and stem cell factor (SCF) have dominant roles at this stage of triple negative (TN) thymocyte development. Because there is no age-associated decrease in the number of CD44+CD25-CD3-CD4-CD8- cells, this study investigated whether alterations in apoptosis within the TN pathway accounted for diminishing thymocyte numbers with age. Here we show significant age-associated increases in apoptotic TN thymocytes, specifically within CD44+CD25+ and CD44-CD25+ subpopulations, known to be the location of TCR {beta}-chain rearrangement. IL-7 added to TN cultures established from old mice significantly both reduces apoptosis and increases the percentage of live cells within CD44+CD25+ and CD44-CD25+ subpopulations after 24 h, with prosurvival effects remaining after 5 days. SCF failed to demonstrate prosurvival effects in old or young cultures, and IL-7 and SCF together did not improve upon IL-7 alone. IL-7R expression did not decline with age, ruling out the possibility that the age-associated increase in apoptosis was attributed to reduced IL-7R expression. Compared with PBS, treatment of old mice with IL-7 produced significant increases in live TN cells. By comparison, treatment with SCF failed to increase live TN numbers, and IL-7 and SCF together failed to significantly improve thymopoiesis above that shown by IL-7 alone. Thus, treatment with IL-7 alone can reverse the age-associated defect in TN thymocyte development revealed by in vitro studies to be located at the stages of TCR {beta}-chain rearrangement.




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