Abstract
AbstractLymphocyte numbers need to be quite tightly regulated. It is generally assumed that lymphocyte production and survival rates increase homeostatically when lymphocyte numbers decrease. This widely-accepted concept is largely based on experiments in mice. In humans, lymphocyte reconstitution usually occurs very slowly, which challenges the idea that density dependent homeostasis aids recovery from lymphopenia. Using in vivo deuterium labelling, we quantified lymphocyte production and survival rates in patients who underwent an autologous hematopoietic stem cell transplantation (autoHSCT). We indeed found that the production rates of most T-cell and B-cell subsets in autoHSCT-patients were 2 to 8-times higher than in healthy controls. These increased lymphocyte production rates went hand in hand with a 3 to 9-fold increase in cell loss rates, and both rates did not normalize when cell numbers did. This challenges the concept of homeostatic regulation of lymphocyte production and survival rates in humans.
Publisher
Cold Spring Harbor Laboratory
Reference43 articles.
1. Changes in blood lymphocyte numbers with age in vivo and their association with the levels of cytokines/cytokine receptors;Immun. Ageing,2016
2. Aging and Cytomegalovirus Infection Differentially and Jointly Affect Distinct Circulating T Cell Subsets in Humans
3. Population Biology of Lymphocytes: The Flight for Survival
4. T cell repopulation from functionally restricted splenic progenitors: 10,000-fold expansion documented by using limiting dilution analyses;J. Immunol,1984
5. The stable and permanent expansion of functional T lymphocytes in athymic nude rats after a single injection of mature T cells;J. Immunol,1987