Stress-induced alterations in the programmed natural cycles of post-natal lymphoid organ development in C57BL/6 mice: Evidence for a regulatory feedback relationship between bone marrow and thymus

This study investigated some effects of weaning and immobilization stress in C57BL/6 mice aged 22–68 days, i.e., over a period including activation of the hypothalamus–pituitary–adrenal (HPA) axis and puberty. Specifically, the study evaluated the evolution, over the referred age interval, of a set of variables (body, thymus, spleen and axillary lymph nodes weights, the proportion of lymphoid cells in the bone marrow, the relative chemoattraction capacity of thymic supernatants for lymphoid cells and the migratory capacity of bone marrow lymphoid cells) in either weaned mice or weaned mice subjected to immobilization stress, compared to “non-stressed” unweaned mice. Cyclic patterns, observed for most variables in unweaned mice, were especially pronounced in two cases: the relative migratory capacity of bone marrow lymphoid cells collected at different ages towards neonatal thymic supernatant, and the relative chemoattraction capacity of thymic supernatants of different ages as tested against a sample of bone marrow lymphoid cells from mice aged 35 days. Weaning stress tended to intensify the involution stages of the cycles in thymus, spleen and lymph node weight, but increased the relative proportion of lymphoid cells in the bone marrow cell population. Both types of exogenous stress tended to affect cycle phase, i.e., cycle peaks and troughs were shifted in time. Correlations were observed between patterns seen in the thymus and bone marrow, suggesting the existence of an autoregulatory feedback loop governing pre-T cell migration and bone marrow/thymus homeostasis. These results also suggest that exogenous stress acts as a non-programmed regulator, modulating the naturally programmed cyclic patterns.