European Journal of Clinical Investigation (2005) 35, 380–387 © 2005 Blackwell Publishing Ltd Blackwell Publishing, Ltd. Age-related thymic activity in adults following chemotherapy-induced lymphopenia P. P. Sfikakis, G. M. Gourgoulis, L. A. Moulopoulos, G. Kouvatseas, A. N. Theofilopoulos * and M. A. Dimopoulos Athens University Medical School, Athens, Greece, and * The Scripps Research Insitute, La Jolla, CA Abstract 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. Keywords Aging, immune senescence, lymphopenia, T-cell, thymus. Eur J Clin Invest 2005; 35 (6): 380–387 Introduction The age-related decline of the immune system’s capacity to regenerate a depleted lymphocyte pool is considered a cen- tral obstacle to clinical progress for HIV-1 infection and bone marrow transplantation, as well as to the development of T-cell immune-based cancer therapies [1,2]. Moreover, inefficient reconstitution of the peripheral lymphocyte pool in adults recovering from intensive chemotherapy may result in increased susceptibility to infection [3,4], and decreased efficacy of vaccines [5]. As lymphopenia-inducing cytotoxic drugs are the mainstay of cancer treatments, a greater understanding of the immune system’s capacity to restore a depleted T-cell pool in the elderly is important [1,2,6 –10]. First Department of Propedeutic Medicine, Laikon Hospital (P. P. Sfikakis, G. M. Gourgoulis, G. Kouvatseas); Department of Clinical Therapeutics, Alexandra Hospital (G. M. Gourgoulis, G. Kouvatseas, M. A. Dimopoulos); Department of Radiology, Areteion Hospital, Athens University Medical School, (L. A. Moulopoulos), Athens, Greece; Immunology Department, The Scripps Research Institute, La Jolla, CA (A. N. Theofilopoulos). Correspondence to: P. P. Sfikakis, MD, First Department of Propedeutic Medicine, Laikon Hospital, 3, Amaryllidos Str, 15452, Athens, Greece. Tel.: +32 10 7258555; fax: +32 10–7485965; e-mail: psfikakis@med.uoa.gr Received 28 December 2004; accepted 21 March 2005