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.
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.
Authors: Ann P Chidgey; Natalie Seach; Jarrod Dudakov; Maree V Hammett; Richard L Boyd Journal: Semin Immunopathol Date: 2008-11-04 Impact factor: 9.623
Authors: J B Langenhorst; C van Kesteren; E M van Maarseveen; T P C Dorlo; S Nierkens; C A Lindemans; M A de Witte; A van Rhenen; R Raijmakers; M Bierings; J Kuball; A D R Huitema; J J Boelens Journal: Blood Adv Date: 2019-07-23
Authors: Luis M Vence; Chiyu Wang; Himabindu Pappu; Ryan E Anson; Tejal A Patel; Priscilla Miller; Roland Bassett; Gregory Lizee; Willem W Overwijk; Krishna Komanduri; Cara Benjamin; Gladys Alvarado; Sapna P Patel; Kevin Kim; Nicholas E Papadopoulos; Agop Y Bedikian; Jade Homsi; Wen-Jen Hwu; Richard Boyd; Laszlo Radvanyi; Patrick Hwu Journal: J Immunother Date: 2013-05 Impact factor: 4.456
Authors: Afam A Okoye; Mukta Rohankhedkar; Audrie L Konfe; Chike O Abana; Matthew D Reyes; Joseph A Clock; Derick M Duell; Andrew W Sylwester; Partha Sammader; Alfred W Legasse; Byung S Park; Michael K Axthelm; Janko Nikolich-Žugich; Louis J Picker Journal: J Immunol Date: 2015-09-28 Impact factor: 5.422