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

• Published in: Blood 1997-05, Vol.89 (10), p.3700-3707
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age Factors; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biological and medical sciences; CD4-Positive T-Lymphocytes - pathology; CD8-Positive T-Lymphocytes - pathology; Chemotherapy; Child; Child, Preschool; Female; Follow-Up Studies; Hematopoiesis - drug effects; Humans; Infant; Lymphocyte Count - drug effects; Lymphopenia - chemically induced; Lymphopenia - pathology; Male; Medical sciences; Neoplasm Recurrence, Local - immunology; Neoplasm, Residual; Neoplasms - drug therapy; Neoplasms - immunology; Neoplasms - pathology; Pharmacology. Drug treatments; Thymus Gland - pathology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v89.10.3700

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.