Distinctions between CD8+ and CD4+ T-cell regenerative pathways result in prolonged T-cell subset imbalance after intensive chemotherapy
| Autor: | C L, Mackall, T A, Fleisher, M R, Brown, M P, Andrich, C C, Chen, I M, Feuerstein, I T, Magrath, L H, Wexler, D S, Dimitrov, R E, Gress |
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| Rok vydání: | 1997 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male Neoplasm Residual Adolescent Age Factors Infant Thymus Gland CD8-Positive T-Lymphocytes Hematopoiesis Child Preschool Lymphopenia Neoplasms Antineoplastic Combined Chemotherapy Protocols Humans Female Lymphocyte Count Neoplasm Recurrence Local Child Follow-Up Studies |
| Zdroj: | Blood. 89(10) |
| ISSN: | 0006-4971 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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