Age-related thymic activity in adults following chemotherapy-induced lymphopenia

Background The potential role of the adult thymus in T‐cell homeostasis subsequent to lymphopenia remains the subject of debate. We examined whether thymic activity contributes to reconstitution of the peripheral T‐cell pool, a critical process for patients recovering from antineoplastic therapy. Methods In selected patients with various neoplastic diseases we assessed peripheral blood lymphocyte subsets by flow‐cytometry, including thymus‐derived, CD4+ T cells expressing the CD45RA molecule, and thymic size rebound by CT scan before, and 3, 6 and 12 months after completion of cytotoxic therapy. Results Adult patients (n = 21, mean age of 30 years, range 18–49) had higher baseline numbers of B and lower numbers of NK cells than elderly patients (n = 15, mean age of 79 years, range 70–91), while total T‐cell numbers did not differ. Despite the reduction of lymphocyte counts being comparable in the adult (mean of 45%) and elderly (mean of 49%) groups, occurring at, or near, completion of treatment, an enlargement of the previously atrophic thymus was evident in 63% of the adult, but in none of the elderly, subjects. In 22 patients who remained active disease‐free during the following year, B cells and NK cells recovered to pretreatment levels as soon as at 3 months, whereas overall T‐cell recovery occurred at 6 months post‐treatment. Thymic rebound, observed in 11 of 22 patients who were of younger age, correlated significantly with a faster and more complete recovery of CD45RA+ CD4+ (mainly helper‐naïve) T cells. Conclusion The adult thymus appears capable of regeneration, at least up to middle age, contributing significantly to the reconstitution of the peripheral T‐cell pool following chemotherapy‐induced lymphopenia. In advanced age, however, although peripheral homeostatic pathways appear intact, regeneration of the naïve repertoire is incomplete.