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Distinctions between CD8+ and CD4+ T-cell regenerative pathways result in
prolonged T-cell subset imbalance after intensive chemotherapy
CL Mackall, TA Fleisher, MR Brown, MP Andrich, CC Chen, IM Feuerstein, IT Magrath, LH Wexler, DS Dimitrov and RE Gress
Laboratory of Mathematical Biology, National Cancer Institute, and the
Clinical Pathology Department, National Institutes of Health, Bethesda, MD
20892-1928, USA.
Rapid recovery of CD4+ T cells after intensive chemotherapy is limited by
an age-dependent decline in thymopoiesis. Here we sought to determine
whether similar limitations exist for CD8+ T-cell regeneration. After
intensive chemotherapy, CD8+ T cells had a faster effective doubling time
than CD4+ T cells (median, 12.6 v 28.2 days, P < .05). Accordingly, at 3
months posttherapy, mean CD8+ T-cell number had returned to baseline,
whereas mean CD4+ T-cell number was only 35% of pretherapy values (P <
.05). These differences were primarily due to very rapid expansion of
CD8+CD57+ and CD8+CD28- subsets. At 3 months posttherapy, there was no
relationship between age and CD8+ T-cell number (R = -.02), whereas CD4+
T-cell number was inversely related to age (R = -.66) and there were no
discernible differences in CD8+ recovery among patients with or without
thymic enlargement, whereas CD4+ recovery was enhanced in patients with
thymic enlargement after chemotherapy (P < .01). Therefore
thymic-independent pathways of T-cell regeneration appear to rapidly
regenerate substantial numbers of CD8+, but not CD4+ T cells, resulting in
prolonged T-cell subset imbalance after T-cell depletion. These inherent
distinctions between CD4+ v CD8+ T-cell regeneration may have significant
implications for immunotherapeutic strategies undertaken to eradicate
minimal residual neoplastic disease after cytoreductive chemotherapy.
Volume 89,
Issue 10,
pp. 3700-3707,
05/15/1997
Copyright © 1997 by The American Society of Hematology
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