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J Leukoc Biol. 2014 Nov;96(5):767-77. doi: 10.1189/jlb.5MR0114-067R. Epub 2014 May 2.

Impact of sepsis on CD4 T cell immunity.

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Microbiology, Immunology, and Cancer Biology Graduate Program Medical Scientist Training Program.
Department of Pathology and.
Department of Pathology and Interdisciplinary Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
Microbiology, Immunology, and Cancer Biology Graduate Program Center for Immunology, and Department of Urology, University of Minnesota Medical School, Minneapolis, Minnesota, USA; Minneapolis Veterans Administration Health Care System, Minneapolis, Minnesota, USA; and


Sepsis remains the primary cause of death from infection in hospital patients, despite improvements in antibiotics and intensive-care practices. Patients who survive severe sepsis can display suppressed immune function, often manifested as an increased susceptibility to (and mortality from) nosocomial infections. Not only is there a significant reduction in the number of various immune cell populations during sepsis, but there is also decreased function in the remaining lymphocytes. Within the immune system, CD4 T cells are important players in the proper development of numerous cellular and humoral immune responses. Despite sufficient clinical evidence of CD4 T cell loss in septic patients of all ages, the impact of sepsis on CD4 T cell responses is not well understood. Recent findings suggest that CD4 T cell impairment is a multipronged problem that results from initial sepsis-induced cell loss. However, the subsequent lymphopenia-induced numerical recovery of the CD4 T cell compartment leads to intrinsic alterations in phenotype and effector function, reduced repertoire diversity, changes in the composition of naive antigen-specific CD4 T cell pools, and changes in the representation of different CD4 T cell subpopulations (e.g., increases in Treg frequency). This review focuses on sepsis-induced alterations within the CD4 T cell compartment that influence the ability of the immune system to control secondary heterologous infections. The understanding of how sepsis affects CD4 T cells through their numerical loss and recovery, as well as function, is important in the development of future treatments designed to restore CD4 T cells to their presepsis state.


apoptosis; homeostatic proliferation; immune suppression; lymphopenia

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