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.


CONCLUSIONS
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.
Sfikakis
P P
PP
Athens University Medical School, Athens, Greece. psfikakis@med.uoa.gr
Gourgoulis
G M
GM
Moulopoulos
L A
LA
Kouvatseas
G
G
Theofilopoulos
A N
AN
Dimopoulos
M A
MA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D005260:Female; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000096:biosynthesis; D008206:Lymphatic Diseases / Q000473:pathology*; D008231:Lymphopenia / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology / Q000502:physiology
D000970:Antineoplastic Agents; D017493:Leukocyte Common Antigens