To investigate the role of regulatory T cells in the modulation of long-term immune dysfunction during experimental sepsis
. It is well established that sepsis
predisposes to development of a pronounced immunosuppression
. Nevertheless, the mechanisms underlying the immune dysfunction after sepsis
are still not well understood.
Prospective experimental study.
University research laboratory.
Wild-type mice underwent cecal ligation and puncture and were treated with antibiotic during 3 days after surgery. On days 1, 7, or 15 after cecal ligation and puncture, the frequency of regulatory T cells, proliferation of CD4+
T cells and bacterial counts were evaluated. Fifteen days after cecal ligation and puncture, surviving mice underwent secondary pulmonary infection by intranasal inoculation of nonlethal dose of Legionella pneumophila
. Some mice received agonistic glucocorticoid-induced tumor necrosis factor receptor antibody (DTA-1) before induction of secondary infection.
Measurements and Main Results:
Mice surviving cecal ligation and puncture showed a markedly increased frequency of regulatory T cells in thymus and spleen, which was associated with reduced proliferation of CD4+
T cells. Fifteen days after cecal ligation and puncture, all sepsis
-surviving mice succumbed to nonlethal injection of L. pneumophila
. Treatment of mice with DTA-1 antibody reduced frequency of regulatory T cells, restored CD4+
T cell proliferation, reduced the levels of bacteria in spleen, and markedly improved survival of L. pneumophila
These findings suggest that regulatory T cells play an important role in the progression and establishment of immune dysfunction observed in experimental sepsis