T-cell dynamics after high-dose chemotherapy in adults: Elucidation of the elusive CD8+ subset reveals multiple homeostatic T-cell compartments with distinct implications for immune competence

Francesco F. Fagnoni, Laura Lozza, Carlo Zibera, Alberto Zambelli, Luisa Ponchio, Nadia Gibelli, Barbara Oliviero, Lorenzo Pavesi, Roberto Gennari, Rosanna Vescovini, Paolo Sansoni, Gianantonio Da Prada, Gioacchino Robustelli Della Cuna

Research output: Contribution to journalArticlepeer-review

Abstract

Recovery of total T cell numbers after in vivo T-cell depletion in humans is accompanied by complex perturbation within the CD8+ subset. We aimed to elucidate the reconstitution of CD8+ T cells by separate analysis of putative naïve CD95- CD28+, memory CD95+ CD28+ and CD28- T cell compartments after acute maximal depletion by high-dose chemotherapy (HD-ChT) in women with high-risk breast cancer. We found that recovery of putative naïve CD8+ CD95- CD28+ and CD4+ CD95- CD28+ T cells, was compatible with a thymus-dependent regenerative pathway since their recovery was slow and time-dependent, their values were tightly related to each other, and their reconstitution patterns were inversely related to age. By analysing non-naïve T cells, a striking diversion between putative memory T cells and CD28- T cells was found. These latter increased early well beyond normal values, thus playing a pivotal role in total T-cell homeostasis, and contributed to reduce the CD4:CD8 ratio. In contrast, putative memory T cells returned to values not significantly different from those seen in patients at diagnosis, indicating that this compartment may recover after HD-ChT. At 3-5 years after treatment, naïve T cells persisted at low levels, with expansion of CD28- T cells, suggesting that such alterations may extend further. These findings indicate that CD28- T cells were responsible for 'blind' T-cell homeostasis, but support the notion that memory and naïve T cells are regulated separately. Given their distinct dynamics, quantitative evaluation of T-cell pools in patients undergoing chemotherapy should take into account separate analysis of naïve, memory and CD28- T cells.

Original languageEnglish
Pages (from-to)27-37
Number of pages11
JournalImmunology
Volume106
Issue number1
DOIs
Publication statusPublished - 2002

ASJC Scopus subject areas

  • Immunology

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