Open AccessLymph nodes as barriers to T‐cell rejuvenation in aging mice and nonhuman primates
Author(s) -
Thompson Heather L.,
Smithey Megan J.,
Uhrlaub Jennifer L.,
Jeftić Ilija,
Jergović Mladen,
White Sarah E.,
Currier Noreen,
Lang Anna M.,
Okoye Afam,
Park Byung,
Picker Louis J.,
Surh Charles D.,
NikolichŽugich Janko
Publication year - 2019
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12865
Subject(s) - biology , thymic involution , rejuvenation , immune system , spleen , lymphopoiesis , lymph , immunology , naive t cell , involution (esoterism) , t cell , lymphatic system , keratinocyte growth factor , growth factor , stem cell , microbiology and biotechnology , haematopoiesis , pathology , neuroscience , t cell receptor , medicine , receptor , consciousness , biochemistry , genetics
Abstract In youth, thymic involution curtails production of new naïve T cells, placing the onus of T‐cell maintenance upon secondary lymphoid organs (SLO). This peripheral maintenance preserves the size of the T‐cell pool for much of the lifespan, but wanes in the last third of life, leading to a dearth of naïve T cells in blood and SLO, and contributing to suboptimal immune defense. Both keratinocyte growth factor (KGF) and sex steroid ablation (SSA) have been shown to transiently increase the size and cellularity of the old thymus. It is less clear whether this increase can improve protection of old animals from infectious challenge. Here, we directly measured the extent to which thymic rejuvenation benefits the peripheral T‐cell compartment of old mice and nonhuman primates. Following treatment of old animals with either KGF or SSA, we observed robust rejuvenation of thymic size and cellularity, and, in a reporter mouse model, an increase in recent thymic emigrants (RTE) in the blood. However, few RTE were found in the spleen and even fewer in the lymph nodes, and SSA‐treated mice showed no improvement in immune defense against West Nile virus. In parallel, we found increased disorganization and fibrosis in old LN of both mice and nonhuman primates. These results suggest that SLO defects with aging can negate the effects of successful thymic rejuvenation in immune defense.