Distinctions between CD8+ and CD4+ T-cell regenerative pathways result in prolonged T-cell subset imbalance after intensive chemotherapy

Crystal L. Mackall, Thomas A. Fleisher, Margaret R. Brown, Mary P. Andrich, Clara C. Chen, Irwin M. Feuerstein, Ian T. Magrath, Leonard H. Wexler, Dimiter S. Dimitrov, Ronald E. Gress

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3700-3707
Number of pages8
JournalBlood
Volume89
Issue number10
DOIs
StatePublished - May 15 1997

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Mackall, C. L., Fleisher, T. A., Brown, M. R., Andrich, M. P., Chen, C. C., Feuerstein, I. M., Magrath, I. T., Wexler, L. H., Dimitrov, D. S., & Gress, R. E. (1997). Distinctions between CD8+ and CD4+ T-cell regenerative pathways result in prolonged T-cell subset imbalance after intensive chemotherapy. Blood, 89(10), 3700-3707. https://doi.org/10.1182/blood.v89.10.3700