title: T cells are potent early mediators of the host response to sepsis.
abstract: The complex immune response associated with sepsis results in a high rate of morbidity and mortality, despite substantial basic science and clinical advances. Most of the research has centered on the innate immune response, in contrast to the adaptive immune system. This is likely caused by the perceived time frame during which these two responses are understood to mediate their effects. Interestingly, a large degree of lymphocyte apoptosis occurs within the first 24 h of septic insult, suggesting an earlier role for the adaptive response. As we outline, recent studies have shown that reducing T-cell apoptosis dramatically improves survival and bacterial clearance, likely through at least two mechanisms. First, the prevention of lymphocyte apoptosis can limit macrophage phagocytosis of dead T cells and the subsequent production of interleukin 10 and transforming growth factor-β. Second, T lymphocytes can generate interferon-γ and interleukin 17 within the first 24 h that can enhance the early innate immune function sufficient to blunt bacterial infection. However, these and other potent cytokines may have divergent effects that depend upon the severity of sepsis. In more severe sepsis models, activated T cells can increase sepsis morbidity and tissue injury. Conversely, in less severe models, functional T cells decrease mortality and bacterial load. Altogether, the mechanisms underlying protective versus pathological T-cell responses in sepsis remain to be elucidated. As the complex interplay between T cells and innate immune cells is elucidated, novel treatment and therapeutic strategies may be designed that allow for better outcomes in the management of sepsis.
authors.affiliation: Division of Research, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Kasten
authors.forename: Johannes
authors.initials: J
authors.lastname: Tschöp
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Adediran
authors.forename: David A
authors.initials: DA
authors.lastname: Hildeman
authors.forename: Charles C
authors.initials: CC
authors.lastname: Caldwell
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D020381:Interleukin-17; D007371:Interferon-gamma