Sepsis-induced apoptosis causes progressive profound depletion of B and CD4(+) T lymphocytes in humans

Patients with sepsis have impaired host defenses that contribute to the let hality of the disorder. Recent work implicates lymphocyte apoptosis as a po tential factor in the immunosuppression of sepsis. If lymphocyte apoptosis is an important mechanism, specific subsets of lymphocytes may be more vuln erable. A prospective study of lymphocyte cell typing and apoptosis was con ducted in spleens from 27 patients with sepsis and 25 patients with trauma. Spleens from 16 critically ill nonseptic (3 prospective and 13 retrospecti ve) patients were also evaluated. Immunohistochemical staining showed a cas pase-9-mediated profound progressive loss of B and CD4 T helper cells in se psis. Interestingly, sepsis did not decrease CD8 T or NK cells. Although th ere was no overall effect on lymphocytes from critically ill nonseptic pati ents (considered as a group), certain individual patients did exhibit signi ficant loss of B and CD4 T cells. The loss of B and CD4 T cells in sepsis i s especially significant because it occurs during life-threatening infectio n, a state in which massive lymphocyte clonal expansion should exist. Mitoc hondria-dependent lymphocyte apoptosis may contribute to the immunosuppress ion in sepsis by decreasing the number of immune effector cells. Similar lo ss of lymphocytes may be occurring in critically ill patients with other di sorders.