Apoptotic lymphocytes induce progenitor cell mobilization after exercise

Abstract

There is evidence that apoptotic cells and their components have immunmodulatory properties and signaling function. The present study investigated first whether exercise-induced apoptosis and exercise-induced mobilization of progenitor cells are similarly affected by subjects' training status and, second, whether the appearance of dying cells in the circulation might mobilize progenitor cells. CD1 SWISS mice were subjected to a 10-wk endurance training using free wheel running or served as untrained controls. Mice of both groups performed an intensive exercise test after the training period at a velocity corresponding to 80% maximal oxygen uptake for 30 min. Cells from blood and bone marrow were analyzed, and apoptosis and number of progenitor cells determined via flow cytometry. In a second experiment, apoptotic cells were transferred into recipient mice, and mobilization of progenitor cells was analyzed while vital cells served as controls. In untrained animals, the exhaustive exercise was followed by an enhanced rate of annexin V positive CD3(+) cells in blood and bone marrow (P < 0.05), whereas no increase was found in trained mice. Similarly, exercise mobilized Sca-1(+)/c-kit(+) and Sca-1(+)/Flk(+) cells in untrained (P < 0.05) but not trained mice. Furthermore, application of apoptotic cells and their supernatant mobilized Sca-1(+)/c-kit(+) cells into the blood (P < 0.05), whereas Sca-1(+)/Flk(+) cells were not affected. The present study demonstrated that both lymphocyte apoptosis, as well as mobilization of progenitor cells are similarly related to training status. Furthermore, apoptotic cells seem to induce signals that effectively mobilize hematopoietic progenitor cells. The relevance of this effect for the adaptation to exercise stimuli remains to be shown.

There is limited existing evidence to support the common assumption that strenuous endurance exercise bouts impair immune competency

“…In addition, 24 h after exercise, a small number of apoptotic lymphocytes accumulate in bone marrow and blood coinciding with a mobilization of hematopoietic stem cells [17]. Further, injecting apoptotic lymphocytes (or their supernatant) into the bloodstream stimulates hematopoietic stem cell mobilization within 2 h [17]. These observations support the proposal that exercise reverses T cell immunosenescence by 'making immunological space' [18].…”

“…Pivotal research by Kruger and colleagues, using fluorescent cell tracking in rodents, showed that T cells are redeployed to the gut, lungs, and bone marrow following exercise [16] reflecting heightened immune-surveillance at sites where pathogens are likely to be encountered (gut, lungs) and heightened immuno-regulatory activities (in bone marrow). In addition, 24 h after exercise, a small number of apoptotic lymphocytes accumulate in bone marrow and blood coinciding with a mobilization of hematopoietic stem cells [17]. Further, injecting apoptotic lymphocytes (or their supernatant) into the bloodstream stimulates hematopoietic stem cell mobilization within 2 h [17].…”

Is immunosenescence influenced by our lifetime “dose” of exercise?

“…For example, a recent murine study has shown that 24 h after an acute bout of exercise, lymphocytes undergo apoptosis in peripheral blood and bone marrow, which occurs in parallel with an increase of haematopoietic stem cells at these sites (Mooren and Kruger 2015a ). Subsequent experiments showed that after inducing apoptosis in splenic lymphocytes from resting mice by H 2 O 2 exposure, and injecting apoptotic cells (and apoptotic supernatant separately), into the bloodstream of other resting mice, there was a substantial mobilisation of haematopoietic stem cells 2 h later (Mooren and Kruger 2015a ). These mobilised haematopoietic stem cells might travel to the thymus (or potentially extra-thymic sites) and develop into naïve T cells (Radtke et al 2013 ).…”

Intensive Exercise Does Not Preferentially Mobilize Skin-Homing T Cells and NK Cells

“…Similarly, exercise also redeploys T cells to the Peyer"s patches and bone marrow (19,20) and this is likely governed by other site-specific homing molecules like LPAM-1 (37) or VLA-4 (23, 26) rather than CLA. This allocation of certain cells to defined parts of the body might represent a homeostatic immune-surveillance response (10), or, instead, it has been hypothesised that senescent T cells are mobilised into the blood to facilitate their subsequent apoptosis in peripheral tissues (21,34), which may contribute to progenitor cell mobilisation after exercise (24). With regards to cutaneous surveillance against tumours and stressed tissue cells, it is unlikely this is tasked by αβ CD8+ T cells alone (13), and is likely supported by γδ T cells and NK cells, which are highly responsive to acute stress (1,6), and have the migratory capacity to enter cutaneous sites (13).…”